A Study on Hereditary Thrombophilia and Stroke in a Cohort from Sri Lanka.

BACKGROUND: Thrombophilia is an enhanced tendency of arterial or venous blood clot formation. The frequently assessed hereditary thrombophilia mutations associated with stroke are methylenetetrahydrofolate reductase (MTHFR) c.677C>T, Factor V (F5) c.1691G>A (Leiden), and prothrombin (F2) c.20210G>A. The aim of this study was to describe the prevalence of the 3 mutations in ischemic stroke patients in Sri Lanka. METHODS: A database of clinical details and genetic test results of stroke patients referred for thrombophilia screening from June 2006 to April 2014 was maintained prospectively and analyzed retrospectively. RESULTS: A total of 400 ischemic stroke patients (319 arterial, 66 venous, and 15 location unreported) were screened for hereditary thrombophilia. Patients with the MTHFR c.677C>T, F5 c.1691G>A, and F2 c.20210G>A mutations were 17.3%, 3.3%, and .5% of the total cohort, respectively. F5 mutation was present in a statistically significant number of patients with venous thrombosis (P = .005) compared to patients with arterial thrombosis. The MTFHR and F2 mutations showed no such significant association. The mean age of patients with MTHFR, F5, and F2 mutations was 29 (±15), 34 (±11), and 38 (±5.6) years, respectively. CONCLUSION: MTHFR c.677C>T is the predominant mutation and the only mutation that had patients with the homozygous mutant genotype. Venous thrombosis showed a significant association with the F5 c.1691G>A mutation.

17p11.2 and Xq28 duplication detected in a girl diagnosed with Potocki-Lupski syndrome.

BACKGROUND: Potocki-Lupski syndrome is a microduplication syndrome associated with duplication at 17p11.2. Features include facial dysmorphism, moderate to mild cognitive impairment and behavioural abnormalities including autism spectrum disorders. CASE PRESENTATION: We describe a patient from Sri Lanka that was referred for genetic assessment at 4 years of age due to subtle facial dysmorphism and expressive language impairment. She was diagnosed with Potocki-Lupski syndrome through multiplex ligation probe amplification. She carried two duplications; one in 17p11.2 consistent with Potocki-Lupski, and one in Xq including the region for X-linked intellectual disability. CONCLUSION: Despite the absence of expected behavioural symptoms, many features of this patient are in accordance with Potocki-Lupski syndrome. This is the first diagnosed patient in Sri Lanka.

A Survey of Scientist and Policy Makers' Attitudes Toward Research on Stored Human Biological Materials in Sri Lanka.

INTRODUCTION: Stored human samples and the establishment of biobanks are increasing in the world. Along with this there are the questions of ethics that arise such as the correct method of obtaining informed consent for research on stored samples and the policies involved in collaborative research using collected samples. This study is an attempt to evaluate the researchers, academics and policy makers' views on these ethical aspects. METHODS: This was an anonymised study involving a Sri Lankan population of researchers, ethics committee members, and policy makers. A self administered questionnaire was utilised as the study instrument. The questionnaire captured four major areas of interest: demographic characteristics of respondents, their attitudes on informed consent policy, their opinion on rights of collaborating researchers, their attitudes on dealing with international differences in regulatory frameworks. RESULTS: The study included 55 responders with 40/55 (73%) agreeing that donors should receive the option of giving informed consent for future research, with 31/55 (56%) considering multiple- type consent options most appropriate. Regarding the issue of shared samples in collaborative research majority agreed that source country ethics review committee approval was necessary 53/55 (96%). CONCLUSION: The study concludes that sample donors should be given the option of giving advance consent to unspecified future research provided that future research is approved by an ethics committee. In collaborative research, it is necessary to involve ethics committees from donor countries in the research approval process.

Analyzing the necessity of prophylactic antibiotic usage in laparoscopy for uncomplicated gynecologic conditions in Sri Lanka.

AIM: The use of prophylactic antibiotics for laparoscopy of uncomplicated gynecologic conditions is controversial. The aim of this study was to assess whether prophylactic antibiotics is necessary to prevent early postoperative infections and febrile morbidity in elective laparoscopic surgery for benign gynecologic conditions. MATERIAL AND METHODS: A total of 218 patients who underwent laparoscopy for uncomplicated gynecologic conditions were recruited into the study over a 1-year period. Following recruitment into the study, they were divided into two groups (ratio 1:1). Patients were divided into either group A (n = 115) the therapy arm or group B (n = 103) the placebo arm. Group A patients received oral azithromycin 1 g daily for 3 days (i.e. the day before, the day of and the day after the procedure) while group B received placebo therapy. Post-procedural febrile and infection morbidity was analyzed. RESULTS: Morbidity was absent in 91.3% of patients in both groups A and B. The primary outcome measure of postoperative fever was present in eight patients from each group. The secondary outcome measure of postoperative infection was present in one patient from the group that did not receive prophylaxis (group B), who had a surgical site infection. There were no patients with urinary tract infection or pelvic inflammatory disease during the study. CONCLUSION: Antibiotics prophylaxis was not able to achieve statistically significant reduction in postoperative febrile or infective morbidity in laparoscopic gynecologic surgery for benign uncomplicated conditions.

Clinical and genetic features of Huntington disease in Sri Lanka.

BACKGROUND: Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. METHODS: Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. RESULTS: Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (<20 years) and 3 with late onset (>60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p < 0.05). Twenty two (62.8%) had a positive family history, with 13/22 (59.1%) showing a paternal inheritance of the disease. In both groups, those with a family history had a significantly lower age of presentation (p < 0.05). The mean CAG repeat length in patients with FP alleles was 44.6 ± 5 and RP alleles was 37.2 ± 1.1. Age of onset and CAG repeat length of the HTT gene showed significant inverse correlation (p < 0.0005, R2 = 0.727). CONCLUSIONS: The clinical and genetic features seen in patients with Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.

Autosomal dominant hereditary ataxia in Sri Lanka.

BACKGROUND: Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. METHODS: Thirty four patients with autosomal dominant ataxia were recruited. For every patient the following was done: recording of clinical details and genotyping for SCA 1, 2, 3, 6, 7, 8, 12, and 17. RESULTS: Sixty one per cent of the subjects were identified as SCA1. One subject had SCA2, 12 remain unidentified. Mean age at onset was 34.8 ± 10years for SCA1 and 32.7 ± 9.8 for non SCA1. 76% of SCA1 patients and 50% of non SCA1 were using walking aids. Quantification of symptoms and signs were similar in the SCA1 and non SCA1 groups. Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients. Mean CAG repeat length in SCA1 patients was 52.0 ± 3.8, with greater anticipation seen with paternal inheritance. CONCLUSION: SCA1 was the predominant subtype and showed similar phenotype to previous reports. However, disease severity was higher and depression more prevalent in this population than previously described.