Papers by Rohan Jayasekara
Introduction: There are several conditions giving rise to
46, XY disorders of sex development (DS... more Introduction: There are several conditions giving rise to
46, XY disorders of sex development (DSD) with different
modes of inheritance. Therefore definitive diagnosis based
on molecular genetic confirmation would be the ideal to
counsel parents regarding the future implications of the
condition affecting their baby. This is the first report from
Sri Lanka documenting the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Objectives: To describe the socio-demographic and clinical
features and document the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Methods: 46, XY patients with ambiguous genitalia
followed up in the University Unit at the Lady Ridgeway
Hospital, Colombo, and clinically identified as having
androgen insensitivity syndrome (AIS) or a testosterone
biosynthetic defect were recruited for the study. Their
socio-demographic details and clinical features were
documented. Exons 1 to 8 of the AR gene were screened
for mutations by DNA sequencing on a venous blood
sample. SRY gene mutations were also assayed.
Results: Thirty-four patients were studied, 3 of whom
were clinically diagnosed as having complete androgen
insensitivity syndrome (CAIS). Sex of rearing was female
and male in 4 and 30 respectively. AR gene mutations
were detected in 6 patients (17.6%). None of the patients
had SRY gene mutations.
Conclusions: Majority (88%) of the patients were raised
as males. Six patients (17.6%) including the 3 with CAIS,
had genetically confirmed AIS with the detection of AR
gene mutations.
Clinical Pediatric Endocrinology, 2012
Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation i... more Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation in which the gonads of an individual are characterized by the presence of both mature ovarian and testicular tissues. The objective of this paper is to report the clinical, cytogenetic and histopathological findings in Sri Lankan patients diagnosed with OT-DSD who were referred to the Human Genetics Unit for cytogenetic evaluation during 2005 to 2011. Five patients had histopathologically confirmed OT-DSD. Their ages at presentation ranged from 2 mo to 47 yr. Clinical symptoms varied from ambiguous genitalia and inguinal hernias at birth to a lower abdominal mass presenting in adulthood. All 5 were reared as phenotypic males. An ovotestis was detected in all cases except one, and the predominant karyotype was 46,XY. The findings in this series of predominantly 46,XY karyotype are in contrast to previously published reports that have reported 46,XX as being the predominant karyotype. It is therefore recommended that individuals with ambiguous genitalia who have the 46,XY karyotype should be thoroughly investigated by ultrasonographic or laparoscopic assessment to determine the exact nature of their internal genital organs. OT-DSD should also be considered in the differential diagnosis of patients with cryptorchidism and inguinal hernia.
Journal of Clinical Research in Pediatric Endocrinology, 2012
Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation i... more Ovotesticular disorder of sex development (OT-DSD) is a rare disorder of sexual differentiation in which the gonads of an individual are characterized by the presence of both mature ovarian and testicular tissues. The objective of this paper is to report the clinical, cytogenetic and histopathological findings in Sri Lankan patients diagnosed with OT-DSD who were referred to the Human Genetics Unit for cytogenetic evaluation during 2005 to 2011. Five patients had histopathologically confirmed OT-DSD. Their ages at presentation ranged from 2 mo to 47 yr. Clinical symptoms varied from ambiguous genitalia and inguinal hernias at birth to a lower abdominal mass presenting in adulthood. All 5 were reared as phenotypic males. An ovotestis was detected in all cases except one, and the predominant karyotype was 46,XY. The findings in this series of predominantly 46,XY karyotype are in contrast to previously published reports that have reported 46,XX as being the predominant karyotype. It is...
Acta obstetricia et gynecologica Scandinavica, Jan 2, 2015
To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single... more To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP) with recurrent miscarriage (RM). Candidate gene association study. Human Genetics Unit, Colombo, Sri Lanka. 202 Sinhalese women with two or more first trimester miscarriages and no living children (cases) and 202 age and ethnicity matched women with no history of miscarriage and having two or more living children (controls). Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. The prevalence of the SNP in cases and controls. The mean age of the women in the RM group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the RM group, 140 (69.3%) had experienced ≥3 first trimester miscarriages. The preval...
International Journal of Infectious Diseases, 2008
Reproductive BioMedicine Online, 2014
P Andraweera).
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2010
Introduction: Preeclampsia (PE) is a common pregnancy complication contributing to maternal and n... more Introduction: Preeclampsia (PE) is a common pregnancy complication contributing to maternal and neonatal morbidity and mortality. The maternal syndrome of preeclampsia is considered part of an increased systemic inflammatory response. We aimed to determine whether ten functional single nucleotide polymorphisms in pro-inflammatory (IL-1A, IL-1B, IL-6) and anti-inflammatory (IL-4, IL-10, IL-1RN) cytokine genes are associated with preeclampsia. Methods: 180 nulliparous Sinhalese women with preeclampsia and 180 normotensive women matched for age, ethnicity, parity and BMI were recruited from two tertiary care hospitals in Colombo. Women with a BMI ≥30 kg/m 2 were excluded. Preeclampsia was diagnosed using international guidelines. Early preeclampsia (n=73) was defined as onset of preeclampsia prior to 34 weeks of gestation. A small for gestational age baby was defined as having a birthweight below the 10th customised birthweight centile (n=102). Peripheral blood was collected from the participants and DNA extracted. Genotypes of IL1A -889C/T, +4845G/T, ILB -511C/T, IL6 -634C/G were determined by the Sequenom MassARRAY system. Results: No significant difference was seen in the BMI of the PE and the control group (PE; 21.0 and Control; 20.7). The frequency of IL1A -889 TT+CT [P=0.013, OR (95% CI) = 1.6 (1.1-2.5)] and +484 TT+GT [P=0.015, OR (95% CI) = 1. 3)] genotypes were significantly increased in women with preeclampsia. The frequency of IL6 -634 CC+GC genotypes were significantly increased in women who developed early onset preeclampsia (P=0.01, OR (95% CI) = 1.9 (1.1-3.6). The frequency of IL1B -511 AA+GA genotypes were significantly increased in preeclamptic pregnancies resulting in the delivery of a small for gestational age baby [P=0.021, OR (95% CI) = 1.7 (1.0-2.7)]. All results remained significant after correction for potential confounding factors. Conclusion: Our results demonstrate that single nucleotide polymorphisms in cytokine genes are associated with preeclampsia in Sinhalese women. Genotypes leading to a pro-inflammatory state confer an increased risk for preeclampsia and may have a role in predicting preeclampsia.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health, 2010
Introduction: Preeclampsia (PE) is a common pregnancy complication contributing to maternal and n... more Introduction: Preeclampsia (PE) is a common pregnancy complication contributing to maternal and neonatal morbidity and mortality. The maternal syndrome of preeclampsia is considered part of an increased systemic inflammatory response. We aimed to determine whether ten functional single nucleotide polymorphisms in pro-inflammatory (IL-1A, IL-1B, IL-6) and anti-inflammatory (IL-4, IL-10, IL-1RN) cytokine genes are associated with preeclampsia. Methods: 180 nulliparous Sinhalese women with preeclampsia and 180 normotensive women matched for age, ethnicity, parity and BMI were recruited from two tertiary care hospitals in Colombo. Women with a BMI ≥30 kg/m 2 were excluded. Preeclampsia was diagnosed using international guidelines. Early preeclampsia (n=73) was defined as onset of preeclampsia prior to 34 weeks of gestation. A small for gestational age baby was defined as having a birthweight below the 10th customised birthweight centile (n=102). Peripheral blood was collected from the participants and DNA extracted. Genotypes of IL1A -889C/T, +4845G/T, ILB -511C/T, IL6 -634C/G were determined by the Sequenom MassARRAY system. Results: No significant difference was seen in the BMI of the PE and the control group (PE; 21.0 and Control; 20.7). The frequency of IL1A -889 TT+CT [P=0.013, OR (95% CI) = 1.6 (1.1-2.5)] and +484 TT+GT [P=0.015, OR (95% CI) = 1. 3)] genotypes were significantly increased in women with preeclampsia. The frequency of IL6 -634 CC+GC genotypes were significantly increased in women who developed early onset preeclampsia (P=0.01, OR (95% CI) = 1.9 (1.1-3.6). The frequency of IL1B -511 AA+GA genotypes were significantly increased in preeclamptic pregnancies resulting in the delivery of a small for gestational age baby [P=0.021, OR (95% CI) = 1.7 (1.0-2.7)]. All results remained significant after correction for potential confounding factors. Conclusion: Our results demonstrate that single nucleotide polymorphisms in cytokine genes are associated with preeclampsia in Sinhalese women. Genotypes leading to a pro-inflammatory state confer an increased risk for preeclampsia and may have a role in predicting preeclampsia.
Sri Lanka Journal of Child Health, 2008
Journal of Maternal-Fetal and Neonatal Medicine, 2013
Objective: To investigate the association of polymorphisms in the vascular endothelial growth fac... more Objective: To investigate the association of polymorphisms in the vascular endothelial growth factor (VEGF) family genes (VEGFA rs699947, VEGFA rs3025039, PGF rs1042886, KDR rs2071559 and KDR rs2305948) with preeclampsia in Sinhalese women in Sri-Lanka. Methods: We conducted a case-control study where 175 nulliparous Sinhalese women with preeclampsia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited in tertiary care maternity hospitals in Sri-Lanka. Preeclampsia was diagnosed using international guidelines. DNA extracted from peripheral venous blood and was genotyped using the Sequenom MassARRAY system. χ 2 -test was used to compare the distribution of allele and genotype frequencies between the cases and the control subjects. Results: The frequency of PGF rs1042886 variant allele (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-2.1) and dominant genotype model (aOR 1.6, 95% CI 1.0-2.4) were increased in preeclamptic women compared to controls. VEGFA rs699947, VEGFA rs3025039, KDR rs2071559, and KDR rs2305948 polymorphisms were not associated with preeclampsia. Conclusion: Maternal PGF rs1042886 polymorphism is associated with preeclampsia in Sinhalese women in Sri-Lanka.
New Genetics and Society, 2005
To date, relatively little is known about the ethical, legal and social responses to recent advan... more To date, relatively little is known about the ethical, legal and social responses to recent advances in reproductive and genetic technology outside Europe and North America. This article reports on a survey carried out among doctors (n=278) and medical students (n=1256) in Sri Lanka to find out more about their responses to novel interventions in human reproduction such as In-Vitro Fertilization, Pre-Implantation Genetic Diagnosis and genetic engineering. In the first part of the paper comparisons are drawn between this survey and a survey carried out in 1985 which also considered issues surrounding amniocentesis and therapeutic termination. The second part of the paper deals with more recent developments. The analysis reveals high levels of support for the use of new technologies in treating infertility and identifying genetic disorders. However, differences are apparent among the major religious communities represented in the sample and these are particularly in evidence in relation to prenatal genetic diagnosis. An important theme throughout both surveys is the continuing tension surrounding State policy and termination of pregnancy and the implications this has for the development of screening and counseling services where genetic disorders are concerned.
Molecular Human Reproduction, 2007
Journal of Reproductive Immunology, 2010
Journal of Obstetrics and Gynaecology Research, 2009
The aim of these investigations was to study three candidate genes for pre-eclampsia -epidermal g... more The aim of these investigations was to study three candidate genes for pre-eclampsia -epidermal growth factor (EGF), transforming growth factor alpha, and angiotensinogen -in pregnant Sinhalese women from Sri Lanka, the first such study undertaken in this ethnic group. Reproducibility of results of genetic association studies of candidate genes for pre-eclampsia has not been consistent across populations. One of the factors that may contribute to such inconsistencies is genetic stratification due to population admixture. We therefore compared the allele frequencies of these candidate genes in healthy Sri Lankan subjects from three ethnic groups -Sinhalese, Sri Lankan Tamils and Moors -and in white Western Europeans. Methods: Allele frequencies were established in 80 subjects from each of four populations (Sinhalese, Sri Lankan Tamils, and Moors in Sri Lanka and white Western Europeans in the UK). A further 175 Sinhalese women with pre-eclampsia and 171 normotensive Sinhalese controls were genotyped at eight single nucleotide polymorphisms in the candidate genes. Results and Discussion: In all genes haplotype and allele frequencies were comparable within the three Sri Lankan populations, but differed significantly from those in the white Western European population. Consequently cryptic population stratification is unlikely to have significant effects on allele or haplotype frequencies of the genes examined in this case-control study of Sinhalese women which showed a marginal association for EGF haplotypes and genotypes with pre-eclampsia (P = 0.031). This association requires replication in other populations.
Journal of Obstetrics and Gynaecology Research, 2007
To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-ecla... more To report the occurrence of morbidity and mortality associated with carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women with strictly defined disease. A phenotyping database of 180 nulliparous women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were recruited for a study into genetics of pre-eclampsia was analyzed. Women who developed pre-eclampsia had significantly higher systolic blood pressure (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered at <34 weeks, at 34-36 weeks, and at term, respectively. 78% required a cesarean section. Complications included SBP > or = 160 mmHg (75.5%); DBP > or = 110 mmHg (83.8%); proteinuria > or =3 + (150 mg/dL) in the urine protein heat coagulation test (87%); renal failure requiring dialysis (2%); platelet counts <100 x 10(9)/L (13%); > or =70 U/L in aspartate and/or alanine aminotransaminase (15%); placental abruption (4%); eclampsia (9%); and one maternal death. Maternal complications indicative of severe disease, apart from the incidence of SBP > or = 160 mmHg and DBP > or = 110 mmHg, were not significantly different in early and late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48% of babies were small for gestational age. Only 80 of 135 babies of women with pre-eclampsia whose condition could be confirmed at 6 weeks post-partum were alive. Pre-eclampsia in Sinhalese women is associated with severe maternal morbidity and fetal morbidity and mortality, suggesting that modification of the Western diagnostic criteria and/or guidelines for medical care may be necessary. There is an urgent need to improve neonatal intensive care services in Sri Lanka.
Journal of Molecular and Genetic Medicine, 2011
International Journal of Infectious Diseases, 2008
Human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a pathogen more usually associa... more Human cutaneous leishmaniasis (CL) caused by Leishmania donovani, a pathogen more usually associated with visceral leishmaniasis, is now endemic in Sri Lanka. This report details the characteristics of 200 patients with locally acquired CL, who were recruited prospectively for an ongoing study into the genetic susceptibility to CL in Sri Lanka. In each case, the CL was confirmed by the demonstration of amastigotes in a direct smear and/or promastigotes in a culture. Although only 82% of the Sri Lankan population is Sinhalese, all 200 patients belonged to this ethnic group. The patients had a median age of 32 years (range54-80 years). Most of them each had a single, non-tender, non-itching and dry lesion which had started as a papule and then gradually enlarged and ulcerated, with changes in the surrounding skin. None of the patients had any signs of systemic disease. Eleven (5.5%) each had at least one other affected family member. Patients with multiple lesions were most likely to be found in families with more than one affected member (P50.002) but multiple lesions were not associated with diabetes mellitus (P.0.05). Although the results of passive detection under-estimate the true occurrence of a disease, the present data point towards enhanced susceptibility to CL among the Sinhalese and/or certain individuals, possibly determined by genetic factors.
Indian Journal of Human Genetics, 2010
Pentasomy 49,XXXXY is a rare sex chromosome disorder usually presenting with ambigous genitalia, ... more Pentasomy 49,XXXXY is a rare sex chromosome disorder usually presenting with ambigous genitalia, facial dysmorphism, mental retardation and a combination of cardiac, skeletal and other malformations. The incidence of the condition is estimated to be 1 in 85,000 male births. Previously, this condition was identified as a Klinefelter variant. The condition is suspected in a patient, by a combination of characteristic clinical findings, and the diagnosis is confirmed by chromosome culture and karyotyping. In the case we report here, the main presentation of ambiguous genitalia led to a suspicion of a sex chromosome aneuploidy which was subsequently confirmed by chromosomal analysis.
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Papers by Rohan Jayasekara
46, XY disorders of sex development (DSD) with different
modes of inheritance. Therefore definitive diagnosis based
on molecular genetic confirmation would be the ideal to
counsel parents regarding the future implications of the
condition affecting their baby. This is the first report from
Sri Lanka documenting the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Objectives: To describe the socio-demographic and clinical
features and document the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Methods: 46, XY patients with ambiguous genitalia
followed up in the University Unit at the Lady Ridgeway
Hospital, Colombo, and clinically identified as having
androgen insensitivity syndrome (AIS) or a testosterone
biosynthetic defect were recruited for the study. Their
socio-demographic details and clinical features were
documented. Exons 1 to 8 of the AR gene were screened
for mutations by DNA sequencing on a venous blood
sample. SRY gene mutations were also assayed.
Results: Thirty-four patients were studied, 3 of whom
were clinically diagnosed as having complete androgen
insensitivity syndrome (CAIS). Sex of rearing was female
and male in 4 and 30 respectively. AR gene mutations
were detected in 6 patients (17.6%). None of the patients
had SRY gene mutations.
Conclusions: Majority (88%) of the patients were raised
as males. Six patients (17.6%) including the 3 with CAIS,
had genetically confirmed AIS with the detection of AR
gene mutations.
46, XY disorders of sex development (DSD) with different
modes of inheritance. Therefore definitive diagnosis based
on molecular genetic confirmation would be the ideal to
counsel parents regarding the future implications of the
condition affecting their baby. This is the first report from
Sri Lanka documenting the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Objectives: To describe the socio-demographic and clinical
features and document the presence of mutations in the
androgen receptor (AR) gene in a cohort of children with
46, XY DSD.
Methods: 46, XY patients with ambiguous genitalia
followed up in the University Unit at the Lady Ridgeway
Hospital, Colombo, and clinically identified as having
androgen insensitivity syndrome (AIS) or a testosterone
biosynthetic defect were recruited for the study. Their
socio-demographic details and clinical features were
documented. Exons 1 to 8 of the AR gene were screened
for mutations by DNA sequencing on a venous blood
sample. SRY gene mutations were also assayed.
Results: Thirty-four patients were studied, 3 of whom
were clinically diagnosed as having complete androgen
insensitivity syndrome (CAIS). Sex of rearing was female
and male in 4 and 30 respectively. AR gene mutations
were detected in 6 patients (17.6%). None of the patients
had SRY gene mutations.
Conclusions: Majority (88%) of the patients were raised
as males. Six patients (17.6%) including the 3 with CAIS,
had genetically confirmed AIS with the detection of AR
gene mutations.