Vikas Malhotra

Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss.

In a study of 530 individuals with non-syndromic, sensorineural hearing loss, we identified 18 mutations at connexin 26 (Cx26), four of which are novel (−23G>T, I33T, 377_383dupTCCGCAT, W172R) and the remaining 14 (ivs1+1G>A, M1V, 35delG, W24X, I35S, V37I, R75W, W77X, 312del14, E120del, Q124X, Y136X, R143W, R184P) being mutations previously described. To gain insight into functional consequences of these mutations, cellular localization of the mutant proteins and their ability to permit lucifer yellow transfer between cells was studied in seven of them (W24X, I33T, I35S, R75W, E120del, W172R and R184P). I35S and R184P showed impaired trafficking of the protein to the plasma membrane. I33T, R75W, E120del and W172R showed predominantly membrane localization but did not form functional gap junction channels. Surprisingly, W24X, a protein-truncating mutation, apparently permits formation of a full-length protein, perhaps due to a stop codon read-through mechanism. These results provide further evidence that Cx26 mutations affect gap junction activity by mis-regulation at multiple levels.

Non-syndromic hearing impairment in India: high allelic heterogeneity among mutations in TMPRSS3, TMC1, USHIC, CDH23 and TMIE.

Mutations in the autosomal genes TMPRSS3, TMC1, USHIC, CDH23 and TMIE are known to cause hereditary hearing loss. To study the contribution of these genes to autosomal recessive, non-syndromic hearing loss (ARNSHL) in India, we examined 374 families with the disorder to identify potential mutations. We found four mutations in TMPRSS3, eight in TMC1, ten in USHIC, eight in CDH23 and three in TMIE. Of the 33 potentially pathogenic variants identified in these genes, 23 were new and the remaining have been previously reported. Collectively, mutations in these five genes contribute to about one-tenth of ARNSHL among the families examined. New mutations detected in this study extend the allelic heterogeneity of the genes and provide several additional variants for structure-function correlation studies. These findings have implications for early DNA-based detection of deafness and genetic counseling of affected families in the Indian subcontinent.

Prevalence of preventable ear disorders in over 15,000 schoolchildren in northern India.

BACKGROUND There is a considerable scarcity of reliable population-based data on the prevalence of preventable ear disorders in developing countries. This study was conducted to determine the prevalence of preventable ear disorders in primary school children (aged 5 to 12 years) in northern India. METHOD A pro forma questionnaire was used to screen 15 718 primary school children in New Delhi for ear disorders. Ear examinations were conducted using otoscopy and impedance audiometry. RESULTS Impacted cerumen was prevalent in 7.93 per cent of schoolchildren, 4.79 per cent suffered from chronic otitis media and 3.06 per cent suffered from otitis media with effusion. Acute otitis media was detected in 0.65 per cent and foreign bodies were found in 0.34 per cent of the children. CONCLUSION Preventable ear diseases posed a significant health problem among children at primary school level. Regular screening of children during this stage would ensure that their school lives were not affected by hearing impairments or preventable ear disorders. Information gathered in this study will help in effective treatment prioritisation of ear disorders, planning and resource allocation.

Mediastinal enteric duplication cyst containing aberrant pancreas

Objective : The purpose of the study is to report a unique association of clinical and pathological findings in a neonate. Foregut enteric duplication cysts-rare developmental anomalies that are associated with midline vertebral fusion anomalies.Methods : We had a neonate with foregut duplication cyst who presented at birth with respiratory distress. The child also had associated communicating hydrocephalus. The patient underwent excision of the duplication cyst alongwith a ventriculo-peritoneal shunt.Result : The excised specimen revealed a duplication cyst lined by aberrant pancreatic tissue.Conclusion : The present case demonstrates histologically the presence of both pancreatic and gastric tissue.

Proboscis lateralis of nose

A rare case of congenital malformation of the nose that was successfully corrected surgically is reported.