Association of serotonin transporter gene polymorphisms with obsessive-compulsive disorder (OCD) in a south Indian population.

Background and Objectives: Serotonin transporter polymorphisms, 5-HTTVNTR and 5-HTTLPR, have been found to be associated with obsessive-compulsive disorder (OCD) and particularly with neurotic characteristics. In the present study we looked for an association between OCD and these polymorphisms in OCD patients and controls of south Indian origin. Methods: 5-HTTVNTR and 5-HTTLPR/rs25531 were genotyped in 93 OCD patients and 92 healthy controls. The allelic distribution and genotype frequency in cases and controls were compared using chi square test. In order to test for the effects of genotype on heterogeneity of the illness, linear regression analysis was undertaken for co-morbid depression status and YBOCS score (severity index). Results: There was no significant association with the 5-HTTVNTR or the 5-HTTLPR polymorphism. No significant association of OCD with the 5-HTTLPR genotype was found even on inclusion of the rs25531 locus, which is part of the transcription factor binding site as reported in earlier studies. However, severity of the illness showed a modest association with the dominant model. Interpretation & conclusions: Our data show that genetic variation in the SLC6A4 gene regulatory region may not have a significant effect on OCD in the present population. Further replication in a large and independent cohort with an equal number of female subjects would help to ascertain if the absence of association in this cohort is due to the nullifying effect of the larger proportion of male subjects in our sample population. The marginal effect of the 5-HTTLPR (A/G) genotype obtained on linear regression with disease severity is suggestive of a potential role for this locus in the disease process.

Deletion analysis of spinal muscular atrophy in southern Indian population.

Background: Proximal spinal muscular atrophy (SMA) is a genetically heterogeneous disease with paresis and muscle atrophy due to loss of anterior horn cell function. The survival of motor neuron gene (SMN) and neuronal apoptosis inhibitory protein (NAIP) play a primary role. Both the gene homologues exist as inverted duplications on Chromosome 5q. The telomeric/functional (SMN1) and the centromeric (SMN2) copies differ from each other in eight nucleotides. The C-->T transition (at Codon 280) within Exon 7 of SMN2 causes disruption of an exonic splicing enhancer (ESE) and/or creates an exonic splicing silencer (ESS) leading to abnormal splicing and a truncated protein. Objective: To determine the molecular genetics of SMN1 and NAIP genes in SMA from southern India. Materials and Methods: In the present study, 37 patients from the neuromuscular disorders clinic of National Institute of Mental Health and Neurosciences were assayed for the deletions in the SMN1 and NAIP genes using PCR-RFLP methods. Results: Among the SMA Type I patients, 43% showed deletions of SMN1 and NAIP. In patients Type II SMA, 57% showed deletions of the SMN1 exons. Conclusion: Thus, deletions were found to occur in 47.8% of the Type I and II patients. Lower sensitivity of gene deletion study in clinically suspected SMA needs further study as clinical diagnosis of SMA is not gold standard. However, the results do correlate with other studies conducted in India.

SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India.

BACKGROUND & OBJECTIVE: Spinocerebellar ataxias (SCAs) are often caused by expansions of CTG/ CAG trinucleotide repeat in the genome. Expansions at the SCA1, 2 and 3 loci are the most frequent, but differences in their relative proportion in regions occur across the world. We carried out this study to assess the occurrence of SCA1, 2 and 3, at a tertiary neuro-psychiatric center in Bangalore, Karnataka. METHODS: Probands (N=318) who were diagnosed to have an ataxia syndrome (progressive degenerative ataxia of unknown cause) attending the clinical services of the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, were evaluated over a period of three years. Standard protocols were used for both clinical and molecular diagnosis. RESULTS: Genotyping established that SCA1, 2 and 3 accounted for more than one third of the ataxia cases seen in the clinic. In the cases with established family history and autosomal dominant inheritance SCA1 was most prevalent followed by SCA2 and SCA3. INTERPRETATION & CONCLUSION: Our findings suggested SCA1 rather than SCA2 to be the more common mutation in southern India. Large numbers of SCA3 probands were also identified. Differences in prevalence of these syndromes within India need to be explored further for founder effects, correlations with phenotype, and patterns of outcome. Family history was not apparent in almost a fifth of those tested positive, highlighting the value of testing even in the absence of family history. Molecular testing should be extended to cover the other forms of ataxia, of which a large number are now known. Combined efforts to confirm the presence of these less common forms, as well as family studies to detect novel mutations, are necessary in this context in India.