Medical Genetics

Mutations in the GJB2 gene are a major cause of non‐syndromic recessive hearing loss in many countries. In a significant fraction of patients, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity are identified. This paper reports a novel GJB2 mutation, −3438C→T, found in the basal promoter of the gene, in trans with V84M, in a patient with profound hearing impairment. This novel mutation can abolish the basal promoter activity of GJB2. These results highlight the importance of extending the mutational screening to regions outside the coding region of GJB2.

This paper's main contention is that some basically methodological developments in science which are apparently distant and unrelated can be seen as part of a sequential story. Focusing on general inferential and epistemological matters, the paper links occurrences separated by both in time and space, by formal and representational issues rather than social or disciplinary links. It focuses on a few limited aspects of several cognitive practices in medical and biological contexts separated by geography, disciplines and decades, but ...

Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by defective development of teeth, hair, nails and eccrine sweat glands. Both autosomal dominant and autosomal recessive forms of HED have previously been linked to mutations in the ectodysplasin 1 anhidrotic receptor (EDAR) protein that plays an important role during embryogenesis. The coding DNA sequence of the EDAR gene was analyzed in two large Swedish three-generational families with autosomal dominant HED. A non-sense C to T mutation in exon 12 was identified in both families. This disease-specific mutation changes an arginine amino acid in position 358 of the EDAR protein into a stop codon (p.Arg358X), thereby truncating the protein. In addition to the causative mutation two polymorphisms, not associated with the HED disorder, were also found in the EDAR gene. The finding of the p.Arg358X mutation in the Swedish families is the first corroboration of a previously described observation in an American f...

To describe the development and process of consensus used to establish essential genetic and genomic nursing competencies relevant to the entire nursing profession in the United States (US) regardless of academic preparation, role, practice setting, or clinical specialty. Organizing Construct: Rogers' diffusion of innovation theory applied to the adoption of genetics and genomics as the central science for health care. Methods: Multiphased national nursing initiative to develop, refine, and establish with consensus essential competencies in genetics and genomics for all nurses. Findings: Genetics and genomics have emerged as the central science for health care in the 21st century, transforming recommendations for nursing education, practice, regulation and quality control. Conclusion: The Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics indicate the minimal criteria for competency in genetics and genomics for the entire nursing profession in the US.

Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.2, 15q13.3, 16p11.2, 16p13.1 and 22q11 harbour rare but recurrent CNVs that have been uncovered as being important risk factors for several of these disorders. These rearrangements may underlie a broad phenotypical spectrum, ranging from normal development, to learning problems, intellectual disability (ID), epilepsy and psychiatric diseases, such as autism spectrum disorders (ASDs) and schizophrenia (SZ). The highly increased risk of developing neurodevelopmental phenotypes associated with some of these CNVs makes them an unavoidable element in the clinical context in paediatrics, neurology and psychiatry. However, and although finding these risk loci has been the goal of neuropsychiatric genetics for many years, the translation of this recent knowledge into clinical practice has not been trivial. In this article, we will: (1) review the state of the a...

Chromatographic analyses of commercial samples of Romanovsky stains were followed by various chemical and staining studies. Strong banding of chromosomes was found to be favoured by the presence in the stain of high concentrations of Methylene Violet Bernthsen and its immediate homologues. Chromatographic analysis showed that these dyes are present in dry Leishman and Giemsa powders only in small proportion. However, additional active dye may be generated during the process of making up staining solutions from the dry powders, if the methanol used is not contaminated with formic acid and if the period of heating is not too brief.

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Standards and Guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily ensure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular standard or guideline was adopted and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.

Purpose: To describe the genetics-related clinical issues encountered by family physicians, and the medical problems they referred to genetics consultants. Methods: Questionnaires were mailed to a nationwide, random sample of 498 practicing family physicians, asking how many times in the past year they discussed genetic information about 19 familial or genetic conditions with patients and what proportion of the families with each genetic condition were referred for genetics consultation. Factor analysis was used to group the conditions. Results: The response rate was 38% (n ϭ 190). Respondents were similar to nonrespondents except that more were women. Most family physicians reported discussing the genetics of common cancers, cardiovascular disease, and Alzheimer's disease with two or more patients in the past year. Thirteen percent had referred families for genetics assessment of breast-ovarian cancer but only two made genetics referrals for cardiovascular disease or dementia. 25% to 50% of family physicians had addressed genetic issues in at least one family with hemoglobinopathy, a blood clotting disorder, hemochromatosis, mental illness, vision loss or deafness, chromosome abnormality, infertility or pregnancy loss, congenital anomalies, mental retardation, and neurofibromatosis. Most cases were not referred to geneticists. Of respondents, 23% said that genetics consultation is very difficult to obtain or unavailable and 18% listed ethical and social dilemmas related to pursuing genetic diagnosis. Conclusion: Nationwide, family physicians address a variety of genetics issues with patients, most frequently consulting geneticists for perinatal conditions and familial cancers. Access to genetics consultation is more difficult in rural areas. These data may be used in organizing genetics services and in planning professional education programs for primary care clinicians.

We have used a non-isotopic PCR assay based on the chemiluminescent detection of blotted PCR products (CB-PCR) for two dynamic mutation diseases (Huntington's disease and spinocerebellar ataxia type 1). This gives an accurate sizing of alleles and permits a rapid analysis of at risk persons. The system involves PCR of the samples, separation of alleles on polyacrylamidegels, Southern blotting, and hybridisation with specific primers 3' labelled with fluorescein (Fl)-dUTP as probes. CB-PCR retains the isotopic sensitivity for accurate allele determination, avoids isotopic manipulation, and provides the advantages of safety, long term storage of probes, and recycling of hybridisation solutions.

In the mid 1980's, two advances revolutionized Medicine in a way that is comparable only to some of the most important events in the approximately 3,000 years of its history. The first was the introduction of the concept of "positional cloning", i.e. the idea that one can identify genes for human disease though knowing nothing or very little about their function. The second was the discovery of the method of polymerase chain reaction (PCR) which made DNA easier to work with for all biomedical researchers and clinicians. Fresh in the history of Endocrinology were the great discoveries of neuroendocrinology, and even more contemporary and potent, the influence of the then emerging field of molecular endocrinology. Cancer medicine and traditional human genetics were the fields that benefited most from the first applications of the new genomic concepts and technologies. Almost two decades later, and after the first successful applications of positional cloning in Endocrine...

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent nextgeneration sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.

Aim-To determine the gender using mental foramen as landmark on a panoramic radiographs in selected North Gujarat population. Objective-1. To evaluate and compare the superior border of mental foramen to lower border of mandible(S-L) and inferior border of mental foramen to lower border of mandible(I-L) value in males and females bilaterally. 2. To compare the S-L and I-L between right and left side in males and female 3. To utilize above measurements for gender determination. Materials and Method-Sixty panoramic radiographs were selected for the analysis of mental foramen. Tangents were drawn through the superior and inferior borders of the foramen (S-L and I-L respectively) and perpendicular from the tangents to the lower border of the mandible bilaterally. Digital verniar caliper was used for the distance measurement from S-L and I-L. The data obtained was tabulated and subjected to statistical analysis. Result-The analyzed data of study showed that the mean values of comparison of S-L as well as I-L in males and females were significantly higher in males as compared to females. The comparison of SL and IL on right and left side in the same patient was without any significant difference. Conclusion-The results of present study concluded a definite sexual dimorphism in the position of the mental foramen from the base of the mandible; this method can applied in mass disaster where the fragments of mandible are available.

Background: Postpartum hemorrhage is the most common cause of mortality in women with vaginal or cesarean delivery. WHO statistics shows that about 500 thousands women have died of complications related to pregnancy or during childbirth in 2013. haemorrhage probability is the main reason to order blood requests in delivery and cesarean units. The purpose of this study is to evaluate the ratio of cross-matched to transfused blood in pregnant women during one year before and after the implementation of health reform program. Materials and Methods: In this retrospective descriptive study, the requests of blood reserves for pregnant patients with the gravid of 34±7 weeks and the age of 30±16 years old in two periods, before and after the implementation of health reform program were being collected and compared. Blood group antiserums and anti-human globulins with bovine albumins were purchased from LORN company and Baharafshan Company respectively. Results: The total number of requests ...

The advances in next generation sequencing (NGS) technologies have had a significant impact on epigenomic research. The arrival of NGS technologies has enabled a more powerful sequencing based methoddthat is, ChIP-Seqdto interrogate whole genome histone modifications, improving on the conventional microarray based method (ChIP-chip). Similarly, the first human DNA methylome was mapped using NGS technologies. More importantly, studies of DNA methylation and histone modification using NGS technologies have yielded new discoveries and improved our knowledge of human biology and diseases. The concept that cytosine methylation was restricted to CpG dinucleotides has only been recently challenged by new data generated from sequencing the DNA methylome. Approximately 25% of all cytosine methylation identified in stem cells was in a non-CG context. The non-CG methylation was more enriched in gene bodies and depleted in protein binding sites and enhancers. The recent developments of third generation sequencing technologies have shown promising results of directly sequencing methylated nucleotides and having the ability to differentiate between 5-methylcytosine and 5-hydroxymethylcytosine. The importance of 5-hydroxymethylcytosine remains largely unknown, but it has been found in various tissues. 5-hydroxymethylcytosine was particularly enriched at promoters and in intragenic regions (gene bodies) but was largely absent from non-gene regions in DNA from human brain frontal lobe tissue. The presence of 5-hydroxymethylcytosine in gene bodies was more positively correlated with gene expression levels. The importance of studying 5-methylcytosine and 5-hydroxymethylcytosine separately for their biological roles will become clearer when more efficient methods to distinguish them are available.

Book reviews lod scores. Both texts make useful suggestions for further reading, and set problems at the end of each chapter. I was disappointed, however, that little attention was paid to dysmorphology as a component of clinical genetics in either volume, and nor was there a systematic discussion of the potential complications of genetic disorders, and how they may sometimes be avoided.

Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue, often face a long and difficult diagnostic odyssey in pursuit of a name for their condition. Clinicians may dismiss subjective symptoms of chronic pain, thus prolonging patients' odysseys and worsening their care and satisfaction and creating antagonisms in the patient-provider relationship. A greater understanding of patient experiences is necessary in order to decrease burdens of this relationship and to improve care. To that end, we conducted 22 in-depth, semistructured interviews with individuals who had undergone this diagnostic odyssey. We focused on the impact that the odyssey had on their lives, both inside and outside the clinic. Through

γ-hydroxybutyric acid (GHB) causes retrograde amnesia in juveniles and young adults. Earlier, we have reported that in adolescent rat, GHB impairs the hidden platform task performance in the Morris water maze. In the present study, a classical fear conditioning paradigm was used to examine the effects of GHB on the acquisition of contextual conditioning, a hippocampus-dependent associative task, and cued tone conditioning, a hippocampus-independent task, in adolescent rats. Administration of GHB before the presentation of tone-shock pairings dose-dependently disrupted the acquisition of contextual conditioning with no effect on tone conditioning, when conditioned fear was measured 24 h later. Administering GHB prior to testing did not disrupt either contextual or tone conditioning. These results demonstrate that in the adolescent rat exposure to GHB preferentially disrupt hippocampal-dependent learning.

The purpose of a new scientific journal is not only to make new knowledge known, but also to stimulate its use for the benefit of all sectors of society. In a delicate intertwining of social balances, in a stormy sea where every voice generates a wave, the bar must be kept straight. Science does not have to be scary, but ignorance must.

Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

A haplotype map of the human genome The International HapMap Consortium* Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Purpose: Clinical geneticists with a Doctor of Medicine degree face challenges to meet the growing population demand for genetic services. This study was designed to assist the profession with workforce planning by identifying clinically relevant subgroups of geneticists and describing their professional characteristics and clinical practices. Geneticists' patient care productivity is compared across subgroups and other medical specialists. Methods: Part of a comprehensive national study of genetic services and the health workforce, this study uses data from a 2003 survey of geneticists certified by the American Board of Medical Genetics. This study includes 610 clinical geneticists who spend at least 5% of their time in direct patient-care services. An iterative approach was used to identify five subgroups based on the types of new patients seen. We conducted a descriptive analysis of subgroups by demographic, training, professional, and practice characteristics. Results: The subgroups include general (36%), pediatric (28%), reproductive (15%), metabolic (14%), and adult (7%) geneticists. Clinically relevant variations across subgroups were noted in training, professional, and practice parameters. Subgroups vary across patient care hours (median, 15-33 hours/week) and total weekly work hours (52-60 hours). New patient visits (mean, 222-900/year) are higher than follow-up patient visits (mean, 155-405) for all subgroups except metabolic geneticists. Conclusion: Although many geneticists practice as generalist geneticists, this study provides an evidence base for distinguishing clinically relevant subgroups of geneticists. Geneticists provide similar numbers of new patient visits and far fewer follow-up visits than other medical specialists. These findings are relevant to geneticist workforce planning. Genet Med 2006:8(10):603-614.

Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and cu...

Downloaded from www.medrech.com " Rehabilitation of cleft lip and palate patients with a systematic approach " Sherawat Abstract: The oral rehabilitation of lip and palate patients is challenging and many of these patients are suffer if they don't receive sufficient dental treatment. Several techniques, including orthodontic appliances, surgeries, advanced prosthodontic rehabilitation and alveolar bone grafts have been proposed for the oral rehabilitation of these patients. There are still some difficulties in prosthetic rehabilitation of cleft lip and palate patients with conventional prostheses or implant retained prostheses because of insufficient alveolar bone quality and quantity, inadequate soft tissue, and abutment teeth. This paper is an attempt to review the systematic approach in management of cleft lip and palate patients.

The study of inherited monogenic diseases has contributed greatly to our mechanistic understanding of pathogenic mutations and gene regulation, and to the development of effective diagnostic tools. But interest has gradually shifted away from monogenic diseases, which collectively affect only a small fraction of the world's population, towards multifactorial, common diseases. The quest for the genetic variability associated with common traits should not be done at the expense of Mendelian disorders, because the latter could still contribute greatly to understanding the aetiology of complex traits.

Family studies show that the Huntington's disease gene is linked to a polymorphic DNA marker that maps to human chromosome 4. The chromosomal localization of the Huntington's disease gene is the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder.