Genomic medicine aims to improve health using the individual genomic data of people to inform car... more Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translat...
The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome ... more The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitati...
Journal of Genetic Engineering and Biotechnology, 2021
Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinop... more Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients’ HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy c...
A number of genetic disorders present with gingival manifestations which may be in the form of de... more A number of genetic disorders present with gingival manifestations which may be in the form of desquamative, ulcerative lesions or an enlargement of the gingiva. Gingival enlargement is a broad term that refers to gingival overgrowth without cause suggestion i.e. a strictly clinical description of the condition avoiding the flawed pathologic implications of terms used such as hypertrophic gingivitis or gingival hyperplasia. In this chapter we will summarize gingival enlargement that can be attributed to gene pathology. Gingival enlargement may present in some genetic disorders secondary to certain treatments not to actual gene expression e.g. Cystinosis secondary to treatment with cyclosporine-A, or epilepsy treated with phenytoin. This category of genetic disorders will not be discussed in this chapter, but should be considered in the differential diagnosis. Genetic disorders associated with gingival enlargement fall into four main categories according to etiology, clinical present...
OBJECTIVE Investigation of whether the serum level of neopterin can be used as a marker in patien... more OBJECTIVE Investigation of whether the serum level of neopterin can be used as a marker in patients with β-thalassemia, evaluation of its clinical significance and correlation with other laboratory and clinical parameters, including the cytokines interleukin-4 (IL-4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), high sensitive C-reactive protein (hs-CRP) and immunoglobulins. METHOD Study was made of 20 healthy subjects and 56 patients with β-thalassemia, ranging in age from 3 to 25 years. The serum levels of human neopterin, IL-4, IL-6 and TNF-α were determined by the ELISA method, and of hs-CRP and immunoglobulins IgA, IgM, IgG and IgG subclasses IgG1, IgG2, IgG3 and IgG4 by the nephelometric technique. RESULTS The serum levels of neopterin, IL-6, TNF-α and hs-CRP were significantly higher in patients with β-thalassemia than in normal subjects, but the level of IL-4 was the same in the two groups. The levels of immunoglobulins IgA and IgG, as well as IgG subclasses...
Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (... more Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients.
Background Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by e... more Background Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by extremely fragile skin and mucus membranes that blister following minor trauma with scarring and nail dystrophy. The three most common subtypes of epidermolysis bullosa are simplex, junctional, and dystrophic based on the level of tissue separation and site of blister formation. DEB is caused by mutations in COL7A1 gene, which encodes collagen type VII and is transmitted either in dominant or recessive mode. The diagnosis of DEB is based on the characteristic clinical features confirmed histopathologically. Patient and methods The author report a new case of recessive DEB presenting with severe blistering studied through whole exome sequencing. Results Whole exome sequencing revealed a novel homozygous single-base deletion (R2024Gfs*182) in COL7A1 gene. Both parents were confirmed heterozygotes for the mutation by Sanger sequencing. Conclusion Apart from adding a novel frameshift collagen...
BACKGROUND Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease... more BACKGROUND Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients. METHOD This study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA. RESULTS The clinical presentations encompassed, café-au-lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic p...
Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of... more Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of vitamin B12 is questionable. Thus, our purpose was to investigate whether low maternal serum vitamin B12 is associated with an increased risk of NTDs. Prenatal Diagnosis and Clinical Genetics Clinics, National Research Centre, in collaboration with the Radioisotope Department, Nuclear Research Centre, Cairo. The study groups included 36 women who were, or had been, pregnant with a NTD-affected fetus. The control groups comprised 35 healthy women with normal prior or current pregnancy and uncomplicated obstetric histories. Fasting plasma homocysteine, serum folate and cobalamin (vitamin B12) were determined. Odds ratio (OR) and 95% confidence intervals were calculated. The fasting homocysteine was significantly higher in the study groups as compared to the controls. The median serum folate concentrations were similar in cases and controls, while the median vitamin B12 concentrations were...
ABSTRACT Objective: To assess telomeric deletion and the telomerase gene copy number in patients ... more ABSTRACT Objective: To assess telomeric deletion and the telomerase gene copy number in patients with Fanconi anemia (FA) and aplastic anemia. Methods: The study included 10 patients with aplastic anemia (seven FA and three non-FA) and five healthy individuals. All patients were subjected to diepoxybutane test and fluorescent in-situ hybridization study using all human telomeres and TERC and TERT Gene fluorescent in-situ hybridization probes. Results: There was statistically significant difference in telomeric deletion in the patients with FA (P<0.005). Moreover, there was a significant telomeric deletion in patients with aplastic anemia (non-FA) (P<0.016), but there was no significant difference in the deletion between FA and non-FA (P<0.16). In contrast, none of the studied patients exhibited telomerase gene amplification. Conclusion: High values of telomeric end deletions were detected in our patients (FA and non-FA). Our finding confirms that the increase in the enzyme level is caused by other factors than gene amplification.
Binucleated cells show (a) micronucleus and nuclear bud as indicated by the arrows (b) the arrow ... more Binucleated cells show (a) micronucleus and nuclear bud as indicated by the arrows (b) the arrow indicates single micronucleus (c) the arrow indicate double micronuclei and (d) the arrow indicate nucleoplasmic bridge.
ABSTRACT Background Fanconi anemia (FA)-A is the most frequent complementation group and is detec... more ABSTRACT Background Fanconi anemia (FA)-A is the most frequent complementation group and is detected in approximately two-thirds of studied FA patients in most countries. Aim The aim of the study was to screen for the common mutations previously reported in the international literature within exons 27, 34, 38, and 43 of the FANCA gene among Egyptian FA patients. Patients and methods The study included 24 Egyptian FA patients of unrelated consanguineous pedigrees and diagnosed by positive chromosomal breakage studies using diepoxybutane. Ten healthy unrelated individuals of matching age and sex were included as the control group. Genomic DNA amplification, sequencing of exons 27, 34, and 43 of the FANCA gene, and restriction enzyme analysis for the exon 38 3788–3790del mutation were performed for patients and controls. Results No mutations were detected within the studied FANCA gene exons. Conclusion Absence of mutations within the studied exons may denote a different FA molecular pattern in Egyptian patients. Further studies are recommended to define the underlying mutations among Egyptian FA cases as an important step in disease control.
This study presents the prevalence, relative frequency, and analysis of genetic diseases/malforma... more This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation ...
The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of aut... more The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I.
Background: Farber Disease (MIM 228000)1 is a rare AR disorder fi rst described by Sidney Farber ... more Background: Farber Disease (MIM 228000)1 is a rare AR disorder fi rst described by Sidney Farber in 19522. Farber disease is usually recognized by the presence of three symptoms: Painful and progressively deformed joints, nodules under the skin and progressive hoarseness. Other organ systems may also be involved. As with most lysosomal storage diseases, the course of Farber’s Disease is progressive and death typically occurs in infancy. Stiff skin syndrome (SSS) (MIM %184900)1 was fi rst described by Esterly and McKusick as a disorder characterized by thickened and indurated skin of the entire body and limitation of joint mobility with fl exion contractures. Aim of the Study: Diagnosis and clarifi cation of overlapping in the clinical presentation of the studied case. Patients and Methods: Clinical report of an atypically presenting Farber case and analyzing the overlapping manifestations between the two syndromes. Results: Histopathological study was the conclusive diagnostic key i...
Background β-thalassemia is a hereditary blood disorder characterized by reduced or absent synthe... more Background β-thalassemia is a hereditary blood disorder characterized by reduced or absent synthesis of the β chains of hemoglobin resulting in variable disease severity. The high carrier rate of thalassemia in Egypt makes it a priority genetic disease for prevention programs through detection of new cases and screening for carriers. Patients and methods In this study, for the first time in Egypt, tandem mass spectrometry (MS/MS) is used to distinguish patients with β-thalassemia from carriers and controls by calculation of α/β globin peptides ratio, as a contributory step in the management of this disease. The study included 40 patients with β-thalassemia referred from the Hereditary Blood Disorders Clinic, National Research Centre, 32 β-thalassemia carriers (parents of cases), and 34 healthy normal participants of matching age and sex. Dried blood spots from all participants were analyzed using MS/MS, followed by confirmatory molecular analysis. Results The results of MS revealed ...
BACKGROUND This study aimed to delineate the clinical phenotype of patients with 9p deletions, pi... more BACKGROUND This study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion. METHODS We investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD). RESULTS Karyotyping revealed 9p terminal deletion in all patients, and patients 8 and 9 had additional duplication of other chromosomal segments. We used six bacterial artificial chromosome (BAC) clones that could identify the breakpoints at 17-20 Mb from the 9p terminus. Array CGH identified the precise extent of the deletion in six patients; the deleted regions ranged from 16 to 18.8 Mb in four patient...
Infantile systemic hyalinosis (ISH) (MIM 236490) is a rare, progressive, fatal autosomal recessiv... more Infantile systemic hyalinosis (ISH) (MIM 236490) is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues. Our proband was a 4-year-old male with growth retardation, severe labio-gingival enlargement, generalized stiff skin, joint contractures, and intractable diarrhea. We discovered a history of a brother and sister who suffered a more severe disease course. A final diagnosis of systemic hyalinosis was made; we report this case and discuss the clinical and orodental heterogeneity among these siblings in the first report of an Egyptian family with ISH. We present a very rare entity, infantile systemic hyalinosis, a cause of joint contracture, protein-losing enteropathy, and growth retardation in infancy with a review of the relevant literature.
Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like d... more Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migrat...
Genomic medicine aims to improve health using the individual genomic data of people to inform car... more Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translat...
The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome ... more The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitati...
Journal of Genetic Engineering and Biotechnology, 2021
Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinop... more Background Fetal hemoglobin (HbF) induction has shown promise for the treatment of β-hemoglobinopathies. HbF induction in β-thalassemia could overcome ineffective hematopoiesis and thus terminate transfusion dependency for formerly transfusion dependant patients. Several miRNAs have been found to reactivate γ-globin expression and increase HbF. In this study, we aimed to investigate the expression of 4 miRNAs (miR-15a, miR-16-1, miR-96, and miR-486-3p) in high HbF thalassemia patients and correlate their levels with the patients’ HbF levels then, in order to predict the exact role of the studied miRNAs in hematopoiesis, a bioinformatic analysis was carried out. We went through this bioinformatic analysis to determine the network of genes regulated by miRNAs and further investigate the interaction between all of them through their involvement in hematopoiesis. In this study, the differential expression was measured by qRT-PCR for 40 patients with high HbF and compared to 20 healthy c...
A number of genetic disorders present with gingival manifestations which may be in the form of de... more A number of genetic disorders present with gingival manifestations which may be in the form of desquamative, ulcerative lesions or an enlargement of the gingiva. Gingival enlargement is a broad term that refers to gingival overgrowth without cause suggestion i.e. a strictly clinical description of the condition avoiding the flawed pathologic implications of terms used such as hypertrophic gingivitis or gingival hyperplasia. In this chapter we will summarize gingival enlargement that can be attributed to gene pathology. Gingival enlargement may present in some genetic disorders secondary to certain treatments not to actual gene expression e.g. Cystinosis secondary to treatment with cyclosporine-A, or epilepsy treated with phenytoin. This category of genetic disorders will not be discussed in this chapter, but should be considered in the differential diagnosis. Genetic disorders associated with gingival enlargement fall into four main categories according to etiology, clinical present...
OBJECTIVE Investigation of whether the serum level of neopterin can be used as a marker in patien... more OBJECTIVE Investigation of whether the serum level of neopterin can be used as a marker in patients with β-thalassemia, evaluation of its clinical significance and correlation with other laboratory and clinical parameters, including the cytokines interleukin-4 (IL-4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), high sensitive C-reactive protein (hs-CRP) and immunoglobulins. METHOD Study was made of 20 healthy subjects and 56 patients with β-thalassemia, ranging in age from 3 to 25 years. The serum levels of human neopterin, IL-4, IL-6 and TNF-α were determined by the ELISA method, and of hs-CRP and immunoglobulins IgA, IgM, IgG and IgG subclasses IgG1, IgG2, IgG3 and IgG4 by the nephelometric technique. RESULTS The serum levels of neopterin, IL-6, TNF-α and hs-CRP were significantly higher in patients with β-thalassemia than in normal subjects, but the level of IL-4 was the same in the two groups. The levels of immunoglobulins IgA and IgG, as well as IgG subclasses...
Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (... more Hemophilia A (HA) is an inherited X‐linked recessive coagulation disorder caused by factor VIII (F8) deficiency. F8 rearrangements involving intron 22 (int22) and intron 1 (int1) account for almost half of severe HA phenotype also a hotspot exon 14 provides numerous mutational patterns. This study aims to identify F8 gene mutations among Egyptian HA patients.
Background Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by e... more Background Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by extremely fragile skin and mucus membranes that blister following minor trauma with scarring and nail dystrophy. The three most common subtypes of epidermolysis bullosa are simplex, junctional, and dystrophic based on the level of tissue separation and site of blister formation. DEB is caused by mutations in COL7A1 gene, which encodes collagen type VII and is transmitted either in dominant or recessive mode. The diagnosis of DEB is based on the characteristic clinical features confirmed histopathologically. Patient and methods The author report a new case of recessive DEB presenting with severe blistering studied through whole exome sequencing. Results Whole exome sequencing revealed a novel homozygous single-base deletion (R2024Gfs*182) in COL7A1 gene. Both parents were confirmed heterozygotes for the mutation by Sanger sequencing. Conclusion Apart from adding a novel frameshift collagen...
BACKGROUND Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease... more BACKGROUND Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients. METHOD This study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA. RESULTS The clinical presentations encompassed, café-au-lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic p...
Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of... more Folic acid insufficiency is a known risk factor for neural tube defects (NTDs), while the role of vitamin B12 is questionable. Thus, our purpose was to investigate whether low maternal serum vitamin B12 is associated with an increased risk of NTDs. Prenatal Diagnosis and Clinical Genetics Clinics, National Research Centre, in collaboration with the Radioisotope Department, Nuclear Research Centre, Cairo. The study groups included 36 women who were, or had been, pregnant with a NTD-affected fetus. The control groups comprised 35 healthy women with normal prior or current pregnancy and uncomplicated obstetric histories. Fasting plasma homocysteine, serum folate and cobalamin (vitamin B12) were determined. Odds ratio (OR) and 95% confidence intervals were calculated. The fasting homocysteine was significantly higher in the study groups as compared to the controls. The median serum folate concentrations were similar in cases and controls, while the median vitamin B12 concentrations were...
ABSTRACT Objective: To assess telomeric deletion and the telomerase gene copy number in patients ... more ABSTRACT Objective: To assess telomeric deletion and the telomerase gene copy number in patients with Fanconi anemia (FA) and aplastic anemia. Methods: The study included 10 patients with aplastic anemia (seven FA and three non-FA) and five healthy individuals. All patients were subjected to diepoxybutane test and fluorescent in-situ hybridization study using all human telomeres and TERC and TERT Gene fluorescent in-situ hybridization probes. Results: There was statistically significant difference in telomeric deletion in the patients with FA (P<0.005). Moreover, there was a significant telomeric deletion in patients with aplastic anemia (non-FA) (P<0.016), but there was no significant difference in the deletion between FA and non-FA (P<0.16). In contrast, none of the studied patients exhibited telomerase gene amplification. Conclusion: High values of telomeric end deletions were detected in our patients (FA and non-FA). Our finding confirms that the increase in the enzyme level is caused by other factors than gene amplification.
Binucleated cells show (a) micronucleus and nuclear bud as indicated by the arrows (b) the arrow ... more Binucleated cells show (a) micronucleus and nuclear bud as indicated by the arrows (b) the arrow indicates single micronucleus (c) the arrow indicate double micronuclei and (d) the arrow indicate nucleoplasmic bridge.
ABSTRACT Background Fanconi anemia (FA)-A is the most frequent complementation group and is detec... more ABSTRACT Background Fanconi anemia (FA)-A is the most frequent complementation group and is detected in approximately two-thirds of studied FA patients in most countries. Aim The aim of the study was to screen for the common mutations previously reported in the international literature within exons 27, 34, 38, and 43 of the FANCA gene among Egyptian FA patients. Patients and methods The study included 24 Egyptian FA patients of unrelated consanguineous pedigrees and diagnosed by positive chromosomal breakage studies using diepoxybutane. Ten healthy unrelated individuals of matching age and sex were included as the control group. Genomic DNA amplification, sequencing of exons 27, 34, and 43 of the FANCA gene, and restriction enzyme analysis for the exon 38 3788–3790del mutation were performed for patients and controls. Results No mutations were detected within the studied FANCA gene exons. Conclusion Absence of mutations within the studied exons may denote a different FA molecular pattern in Egyptian patients. Further studies are recommended to define the underlying mutations among Egyptian FA cases as an important step in disease control.
This study presents the prevalence, relative frequency, and analysis of genetic diseases/malforma... more This study presents the prevalence, relative frequency, and analysis of genetic diseases/malformations in 73260 individuals. Cases included were ascertained from: Pediatric outpatient clinics of two governmental hospitals and two primary health care centers (PHCCs) in Giza Governorate; Neonatal intensive care unit (NICU) in the selected hospitals and Outpatients Human Genetics Clinics (NRC). 62819 persons visited the outpatients clinics of selected hospitals and PHCCs in Giza governorate. Out of these persons 731 cases (1.16%) proved to have known genetic disorders or malformations. 7755 neonates were delivered in the selected hospitals. Out of these neonates 666 newborns entered NICU and 3% (20 neonates) of them had genetic or congenital disorders. Also, 2686 patients were ascertained from the Human Genetics Clinics, NRC. The overall parental consanguinity rate among the 3417 diagnosed cases was 55%, ranging from 29.5-75%. The study showed a high prevalence of genetic/malformation ...
The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of aut... more The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I.
Background: Farber Disease (MIM 228000)1 is a rare AR disorder fi rst described by Sidney Farber ... more Background: Farber Disease (MIM 228000)1 is a rare AR disorder fi rst described by Sidney Farber in 19522. Farber disease is usually recognized by the presence of three symptoms: Painful and progressively deformed joints, nodules under the skin and progressive hoarseness. Other organ systems may also be involved. As with most lysosomal storage diseases, the course of Farber’s Disease is progressive and death typically occurs in infancy. Stiff skin syndrome (SSS) (MIM %184900)1 was fi rst described by Esterly and McKusick as a disorder characterized by thickened and indurated skin of the entire body and limitation of joint mobility with fl exion contractures. Aim of the Study: Diagnosis and clarifi cation of overlapping in the clinical presentation of the studied case. Patients and Methods: Clinical report of an atypically presenting Farber case and analyzing the overlapping manifestations between the two syndromes. Results: Histopathological study was the conclusive diagnostic key i...
Background β-thalassemia is a hereditary blood disorder characterized by reduced or absent synthe... more Background β-thalassemia is a hereditary blood disorder characterized by reduced or absent synthesis of the β chains of hemoglobin resulting in variable disease severity. The high carrier rate of thalassemia in Egypt makes it a priority genetic disease for prevention programs through detection of new cases and screening for carriers. Patients and methods In this study, for the first time in Egypt, tandem mass spectrometry (MS/MS) is used to distinguish patients with β-thalassemia from carriers and controls by calculation of α/β globin peptides ratio, as a contributory step in the management of this disease. The study included 40 patients with β-thalassemia referred from the Hereditary Blood Disorders Clinic, National Research Centre, 32 β-thalassemia carriers (parents of cases), and 34 healthy normal participants of matching age and sex. Dried blood spots from all participants were analyzed using MS/MS, followed by confirmatory molecular analysis. Results The results of MS revealed ...
BACKGROUND This study aimed to delineate the clinical phenotype of patients with 9p deletions, pi... more BACKGROUND This study aimed to delineate the clinical phenotype of patients with 9p deletions, pinpoint the chromosomal breakpoints, and identify the critical region for trigonocephaly, which is a frequent finding in 9p terminal deletion. METHODS We investigated a cohort of nine patients with chromosome 9p terminal deletions who all displayed developmental delay, intellectual disability, hypotonia, and dysmorphic features. Of them, eight had trigonocephaly, seven had brain anomalies, seven had autistic manifestations, seven had fair hair, and six had a congenital heart defect (CHD). RESULTS Karyotyping revealed 9p terminal deletion in all patients, and patients 8 and 9 had additional duplication of other chromosomal segments. We used six bacterial artificial chromosome (BAC) clones that could identify the breakpoints at 17-20 Mb from the 9p terminus. Array CGH identified the precise extent of the deletion in six patients; the deleted regions ranged from 16 to 18.8 Mb in four patient...
Infantile systemic hyalinosis (ISH) (MIM 236490) is a rare, progressive, fatal autosomal recessiv... more Infantile systemic hyalinosis (ISH) (MIM 236490) is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues. Our proband was a 4-year-old male with growth retardation, severe labio-gingival enlargement, generalized stiff skin, joint contractures, and intractable diarrhea. We discovered a history of a brother and sister who suffered a more severe disease course. A final diagnosis of systemic hyalinosis was made; we report this case and discuss the clinical and orodental heterogeneity among these siblings in the first report of an Egyptian family with ISH. We present a very rare entity, infantile systemic hyalinosis, a cause of joint contracture, protein-losing enteropathy, and growth retardation in infancy with a review of the relevant literature.
Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like d... more Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migrat...
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Papers by Ghada El-Kamah