Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.

Mutations in myosin XVA are responsible for the shaker 2 (sh2) phenotype in mice and nonsyndromic autosomal recessive profound hearing loss DFNB3 on chromosome 17p11.2. We have ascertained seven families with profound congenital hearing loss from Pakistan and India with evidence of linkage to DFNB3 at 17p11.2. We report three novel homozygous mutations in MYO15A segregating in three of these families. In addition, one hemizygous missense mutation of MYO15A was found in one of eight Smith-Magenis syndrome (del(17)p11.2) patients from North America who had moderately severe sensorineural hearing loss.

Human chromosome 11 harbors two Usher type I loci, USHIB and USHIC, which encode myosin VIIA and harmonin, respectively. The USHIC locus overlaps the reported critical interval for nonsyndromic deafness locus DFNB18. We found an IVS12+5G-->C mutation in the USHIC gene, which is associated with nonsyndromic recessive deafness ( DFNB18) segregating in the original family, S-11/12. No other disease-associated mutation was found in the other 27 exons or in the intron-exon boundaries, and the IVS12+5G-->C mutation was not present in 200 representative unaffected individuals ascertained from the same area of India. An exon-trapping assay with a construct harboring IVS12+5G-->C generated wildtype spliced mRNA having exons 11 and 12 and mRNA that skipped exon 12. We conclude that mutations of USHIC can cause both Usher syndrome type IC and nonsyndromic recessive deafness DFNB18.

Several studies have reported that mutations in the GJB2 gene (coding for connexin26) are a common cause of recessive non-syndromic hearing impairment. A GJB2 mutant allele, 35delG, has been found to have a high prevalence in most ethnic groups. Though mutations in the GJB2 gene have been shown to cause autosomal recessive deafness in Indian families, the frequencies of the various mutations are still unknown. In the present study, we analyzed 45 Indian families belonging to three different states, namely, Karnataka, Tamil Nadu, and Delhi with non-syndromic hearing impairment and an apparently autosomal recessive mode of inheritance. All the families were initially screened for three mutations (W24X, W77X, and Q124X) by using allele-specific PCR primers; mutations were confirmed by DNA sequencing. Families that were heterozygous or negative for tested mutations of the GJB2 gene were sequenced directly to identify the complementary mutation and other mutations in GJB2. Four families were homozygous for W24X, constituting around 8.8%. In two families, the affected individuals were compound heterozygotes for W24X; one family (DKB16) carried 35delG with W24X while the other family (DKB7) carried R143W with W24X. We suggest that W24X is a common allele among the mutations screened, causing autosomal recessive non-syndromic hearing impairment (ARNSHI) in the Indian population.

Context:There are scarce data on the prevalence of adult obsessive-compulsive disorder (OCD) in India.Aims:The aim was to study the point prevalence of OCD and subthreshold OCD and its psychosocial correlates among college students in the district of Ernakulam, Kerala, India.Settings and Design:A cross-sectional survey of 5784 students of the age range of 18–25 years from 58 colleges was conducted.Materials and Methods:Students were self-administered the OCD subsection of the Clinical Interview Schedule-Revised, the Composite International Diagnostic Interview for obsessive-compulsive symptoms (OCSs), and other relevant instruments to identify OCD, subthreshold OCD, and related clinical measures.Statistical Analysis:The point prevalence of OCD and subthreshold OCD was determined. Categorical variables were compared using Chi-square/Fisher's exact tests as necessary. Differences between means were compared using the ANOVA.Results:The point prevalence of OCD was 3.3% (males = 3.5%; females = 3.2%). 8.5% students (males = 9.9%; females = 7.7%) fulfilled criteria of subthreshold OCD. Taboo thoughts (67.1%) and mental rituals (57.4%) were the most common symptoms in OCD subjects. Compared to those without obsessive-compulsive symptoms (OCSs), those with OCD and subthreshold OCD were more likely to have lifetime tobacco and alcohol use, psychological distress, suicidality, sexual abuse, and higher attention-deficit/hyperactivity disorder symptom scores. Subjects with subthreshold OCD were comparable to those with OCD except that OCD subjects had higher psychological distress scores and academic failures.Conclusions:OCD and subthreshold OCD are not uncommon in the community, both being associated with significant comorbidity. Hence, it is imperative that both are identified and treated in the community because of associated morbidity.