Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Dissections or prosections: Which method has a better impact on sustainable gross anatomy knowledge?

Background Assessing the level of knowledge of anatomy of undergraduate students four years after their primary anatomy training will give a better indication as to which system of teaching is more effective. We aimed to ascertain which method was more effective at establishing a core of anatomy knowledge that could be recalled after a considerable amount of time. Methods We tested two groups of medical students in their final year on the key concepts of gross anatomy using a question paper that included true-false type questions and identification of anatomical line diagrams. These two batches of students followed a dissection-based curriculum and a newly introduced prosections-based curriculum at the beginning of their medical education. The prosections- based curriculum brought with it a reduction in the in-class teaching and learning activities when compared to the old curriculum. This would in turn reflect how much anatomy knowledge one would possess when they start to practise medicine as a newly qualified doctor and also embark on a postgraduate training programme. The two groups were subjected without prior warning to a question paper that had six questions, each with five true-false statements and four questions on identification and labelling of anatomical line diagrams. Results There was no statistically significant difference in the marks obtained for the true-false type questions between the two groups (p=0.08), but the prosections group obtained higher marks for the diagram identification questions (p=0.02). Conclusion A prosection-based curriculum when compared to a dissection-based curriculum was equally effective at establishing a core of gross anatomy knowledge.

Frequency of Hereditary Hemochromatosis Gene (HFE) Variants in Sri Lankan Transfusion-Dependent Beta-Thalassemia Patients and Their Association With the Serum Ferritin Level.

Introduction: Co-inheritance of hereditary hemochromatosis (HFE) gene variants p. C282Y and p.H63D worsen iron overload in transfusion-dependent thalassemia. Data on the HFE gene variants in Sri Lankan patients with thalassemia have not been extensively studied. This study aimed to analyze the p.C282Y and p.H63D variants in transfusion-dependent beta (ß) and HbE/ß-thalassemia patients and establish an association between these variants and their serum ferritin levels. Materials and Methods: A total of 125 transfusion-dependent ß-thalassemia major and HbE/ß thalassemia patients were tested for the c.845G>A (p.C282Y) and c.187C>G (p.H63D) HFE gene variants using the multiplex Amplification Refractory Mutation System Polymerase Chain Reaction method. For phenotype-genotype correlation, serum ferritin levels, the erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured. The standard descriptive statistics were used for data analysis. Results: The study cohort consisted of transfusion-dependent 123 ß-thalassemia and 2 HbE/ß-thalassemia patients. The p.C282Y variant was not detected in any patient; allele frequency for the wild type (c.845GG) was 100%. Twenty-three patients were heterozygous for the p.H63D variant allele, and the allele frequencies were c.187CC 91.8%, c.187CG 9.2%, and c.187GG 0%. The mean serum ferritin level was relatively higher (mean level 4,987 ng/ml) in the p.H63D heterozygous (c.187CG) group compared to the wild type (c.187CC) group (mean level 4,571 ng/ml), but the difference was statistically not significant (p = 0.865). Among the total study population, CRP, ESR, and serum glutamine aspartate transaminase (SGPT) were elevated in 9 (7.2%), 65 (52%), and 82 (65.6%) patients, respectively. Among the p.H63D c.187CG group, elevated CRP, ESR, and SGPT were present in 5 (5%), 15 (12%), and 18 (14.4%) patients, respectively. The detected sample number was low to correlate with the confounding effect of inflammatory disorders and liver damage on the serum ferritin levels. Conclusions: The HFE gene variant p.C282Y is unlikely to cause iron overload in the Asian ß-thalassemia patients; the rarity of this variant in the study cohort replicates the findings of other South Asian population studies of this variant. The presence of the p.H63D variant could be a potential risk factor for iron overload in the ß-thalassemia patients. A more extensive cohort study is required to validate this finding.

Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.

Introduction: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. Methods: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. Results: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). Conclusion: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette-Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.

Genetic associations of inflammatory bowel disease in a South Asian population.

AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.

The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia.

Pre-eclampsia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-eclampsia. The association of INSR rs2059806 with pre-eclampsia was tested in two cohorts - a Caucasian case control group (123 pre-eclamptic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-eclampsia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-eclamptic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-eclamptic women who delivered small for gestational age infants compared with the uncomplicated pregnancies (10.8% versus 4.2%, OR[95%CI] = 2.8[1.0-7.4], P = 0.03). Thus, it was found that the INSR rs2059806 SNP is also associated with pre-eclampsia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-eclampsia and subsequent vascular and metabolic diseases.

Anatomy of Teaching Anatomy: Do Prosected Cross Sections Improve Students Understanding of Spatial and Radiological Anatomy?

Introduction. Cadaveric dissections and prosections have traditionally been part of undergraduate medical teaching. Materials and Methods. Hundred and fifty-nine first-year students in the Faculty of Medicine, University of Colombo, were invited to participate in the above study. Students were randomly allocated to two age and gender matched groups. Both groups were exposed to identical series of lectures regarding anatomy of the abdomen and conventional cadaveric prosections of the abdomen. The test group (n = 77, 48.4%) was also exposed to cadaveric cross-sectional slices of the abdomen to which the control group (n = 82, 51.6%) was blinded. At the end of the teaching session both groups were assessed by using their performance in a timed multiple choice question paper as well as ability to identify structures in abdominal CT films. Results. Scores for spatial and radiological anatomy were significantly higher among the test group when compared with the control group (P < 0.05, CI 95%). Majority of the students in both control and test groups agreed that cadaveric cross section may be useful for them to understand spatial and radiological anatomy. Conclusion. Introduction of cadaveric cross-sectional prosections may help students to understand spatial and radiological anatomy better.

Extra and Intramuscular Distribution of the Thoracodorsal Nerve with Regard to Nerve Reconstruction Surgeries.

Background The lateral branch of the thoracodorsal nerve (LBTN) is used for nerve transfer in facial, musculocutaneous, axillary nerve injuries and for irreparable C5, C6 spinal nerve lesions and accessory nerve defects. For a successful surgical outcome, the nerve to be used in nerve transfer should be of adequate length and thickness for nerve coaptation. Aim Our objective was to evaluate the length of the LBTN that could be obtained as a donor nerve, externally and within the muscle. Method Eight (8) cadavers with intact upper limbs and thorax which could be positioned in the anatomical position were selected for the study. Cadavers with dissected axillae, brachial plexus or upper limbs were excluded. The thoracodorsal neurovascular bundle was dissected and the number of branches of the thoracodorsal nerve was identified along with its lateral branch. The lateral branch was dissected up to the latissimus dorsi muscle and further intramuscularly. All lengths were measured using a vernier caliper. Results The mean length of the LBTN, up to its first intramuscular branch, is 8.14 cm (range 5.99-12.29 cm). Beyond this, the intramuscular nerve branched further and was of very minute diameter. The mean unbranched intramuscular length of the nerve is 3.36 cm (range 1.3-7.71 cm) which is 41.28% of the total length of the LBTN. Conclusion A significant proportion of the LBTN is found within the latissimus dorsi muscle. This length could potentially be used for direct nerve coaptation by intrafascicular dissection.

Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women.

OBJECTIVE: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women. METHODS: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system. RESULTS: The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preeclamptic women compared with controls {p = 0.04, odds ratio (OR) [95% class interval (CI)] = 1.6 (1.0-2.5)}. The prevalence of the CT genotype [p = 0.01, OR (95% CI) = 1.8 (1.1-2.8)] and the dominant model (CT + TT) [p = 0.03, OR (95% CI) = 1.6 (1.1-2.5)] of the IL1A rs1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p = 0.04, OR (95% CI) = 0.6 (0.4-0.9)] and the dominant model (GA + AA) [p = 0.03, OR (95% CI) = 0.6 (0.4-0.9)] of the MBL1 rs1800450 polymorphism were reduced in preeclamptic women compared to controls. CONCLUSION: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women.

The obesity-related FTO gene variant associates with the risk of recurrent miscarriage.

OBJECTIVE: To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. DESIGN: Candidate gene association study. SETTING: Human Genetics Unit, Colombo, Sri Lanka. POPULATION: A total of 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). METHODS: 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. MAIN OUTCOME MEASURES: The prevalence of the single nucleotide polymorphism in cases and controls. RESULTS: The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. CONCLUSION: The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.

Cytogenetic analysis of chromosomal abnormalities in Sri Lankan children.

BACKGROUND: Cytogenetic analysis is a valuable investigation in the diagnostic work up of children with suspected chromosomal disorders. The objective of this study was to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis. METHODS: Cytogenetic reports of 1554 consecutive children with suspected chromosomal disorders who underwent karyotyping in two genetic centers in Sri Lanka from January 2006 to December 2011 were reviewed retrospectively. RESULTS: A total of 1548 children were successfully karyotyped. Abnormal karyotypes were found in 783 (50.6%) children. Numerical and structural abnormalities accounted for 90.8% and 9.2%, respectively. Down syndrome was the commonest aneuploidy identified. Other various autosomal and sex chromosomal aneuploidies as well as micro-deletion syndromes were also detected. CONCLUSIONS: The prevalence of chromosomal abnormalities in Sri Lankan children undergoing cytogenetic analysis for suspected chromosomal disorders was relatively higher than that in Caucasian and other Asian populations.

Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia.

AIM: This study was aimed at detecting, identifying, quantifying and comparing the bacteria present in the placental tissues of women with pre-eclampsia with that of normotensive pregnant women. MATERIAL AND METHODS: Placental tissue samples were collected from 55 primiparous women with pre-eclampsia (cases) and 55 matched primiparous normotensive pregnant women (controls) at the time of delivery by cesarean section. Genotyping was carried out in two stages. First the samples were screened for the presence of bacteria by polymerase chain reaction (PCR) for the 16S rRNA gene. Next, the samples that were PCR-positive for the 16S rRNA gene were screened by next-generation sequencing on an Illumina MiSeq platform. RESULTS: Seven (12.7%) placental tissue samples from women with pre-eclampsia were PCR-positive. All the placental samples from control women were negative (P = 0.006). The complete microbiome of the seven samples was revealed through next-generation sequencing. The organisms that were present included Bacillus cereus, Listeria, Salmonella, Escherichia (all of which are usually associated with gastrointestinal infection); Klebsiella pneumonia and Anoxybacillus (both of which are usually associated with respiratory tract infections); and Variovorax, Prevotella, Porphyromonas, and Dialister (all of which are usually associated with periodontitis). CONCLUSIONS: This study confirms the presence of bacteria in the placental tissues of a subset of women with pre-eclampsia and supports the role of bacteria in the multifactorial cause of pre-eclampsia.

Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion.

Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children; controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.

A child with a novel de novo mutation in the aristaless domain of the aristaless-related homeobox (ARX) gene presenting with ambiguous genitalia and psychomotor delay.

The objective of this study was to identify disease-causing mutations in a Sri Lankan male child presenting with ambiguous genitalia and psychomotor delay using the exome sequencing approach. A novel mutation in the aristaless-related homeobox (ARX) gene causing a hemizygous nucleotide substitution in exon 5 was identified (NM_139058.2 (ARX): c.1614G>T; p.K538N). This change causes a nonsynonymous substitution in the aristaless domain within the ARX protein which is predicted to be deleterious. This is the first reported case of ambiguous genitalia and psychomotor delay associated with this novel missense mutation within the ARX protein, and it highlights the value of exome sequencing even in sporadic cases.

Polymorphism in the epidermal growth factor gene is associated with pre-eclampsia and low birthweight.

AIM: We have previously reported that polymorphism in the epidermal growth factor (EGF) gene is associated with pre-eclampsia and birthweight based on case-control association studies involving two single nucleotide polymorphisms (SNP). We extended that work to investigate other SNP in the EGF gene for their association with pre-eclampsia and the weight of babies at birth. MATERIAL AND METHODS: A population-based DNA collection was genotyped to determine whether the selected SNP were polymorphic in the study population. In total, 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for the polymorphic SNP using polymerase chain reaction/restriction fragment length polymorphism and MassARRAY Sequenom iPLEX methodology. RESULTS: The rs3756261A, rs4444903G, rs2237051G haplotype was associated with the highest increased risk of pre-eclampsia (odds ratio: 3.70, 95% confidence interval: 1.38-9.94; P = 0.016). The rs3756261A allele was the one that contributed to this high degree of significance. The same allele was present in the haplotype rs3756261A, rs11568943G, rs2237051G, rs11569017A, rs4698803T (likelihood ratio statistic = 20.4671, d.f. = 3, P-value = 0.0001), which was associated with the lower birthweight. CONCLUSIONS: In this study we found further evidence for the association of polymorphism in the EGF gene with pre-eclampsia and the weight of babies at birth and identified rs3756261A>G as the SNP that makes the most significant contribution to this association. Bioinformatic analysis showed that this effect may be mediated by caudal type homeohox-2, a transcriptional repressor expressed in the trophoblast, for which a binding site is created at this polymorphic site when the rs3756261A allele is present.

Anatomical landmarks for safer carpal tunnel decompression: an experimental cadaveric study.

BACKGROUND: Carpal tunnel syndrome is a common presentation to surgical outpatient clinics. Treatment of carpal tunnel syndrome involves surgical division of the flexor retinaculum. Palmar and recurrent branches of the median nerve as well as the superficial palmar arch are at risk of damage. METHODOLOGY: Thirteen cadavers of Sri Lankan nationality were selected. Cadavers with deformed or damaged hands were excluded. All selected cadavers were preserved with the conventional arterial method using formalin as the main preservative. Both hands of the cadavers were placed in the anatomical position and dissected carefully. We took pre- determined measurements using a vernier caliper. We hypothesized that the structures at risk during carpal tunnel decompression such as recurrent branch of the median nerve and superficial palmar arch can be protected if simple anatomical landmarks are identified. We also hypothesized that an avascular area exists in the flexor retinaculum, identification of which facilitates safe dissection with minimal intra operative bleeding. Therefore we attempted to characterize the anatomical extent of such an avascular area as well as anatomical landmarks for a safer carpal tunnel decompression.Ethical clearance was obtained for the study. RESULTS: In a majority of specimens the recurrent branch was a single trunk (n =20, 76.9%). Similarly 84.6% (n = 22) were extra ligamentous in location. Mean distance from the distal border of the TCL to the recurrent branch was 7.75 mm. Mean distance from the distal border of TCL to the superficial palmar arch was 11.48 mm. Mean length of the flexor retinaculum, as measured along the incision, was 27.00 mm. Mean proximal and distal width of the avascular area on TCL was 11.10 mm and 7.09 mm respectively. CONCLUSION: We recommend incision along the radial border of the extended ring finger for carpal tunnel decompression. Extending the incision more than 8.16 mm proximally and 7.75 mm distally from the corresponding borders of the TCL should be avoided. Incision should be kept to a mean length of 27.0 mm, which corresponds to the length of TCL along the above axis. We also propose an avascular area along the TCL, identification of which minimizes blood loss.

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.