Autosomal-recessive (AR) nonsyndromic hearing impairment (NSHI) displays a high degree of genetic heterogeneity with >100 genes identified. Recently, TMEM132E, which is highly expressed in inner hair cells, was suggested as a novel ARNSHI gene for DFNB99. A missense variant c.1259G>A: p.(Arg420Gln) in TMEM132E was identified that segregated with ARNSHI in a single Chinese family with two affected members. In the present study, a family of Pakistani origin with prelingual profound sensorineural hearing impairment displaying AR mode of inheritance was investigated via exome and Sanger sequencing. Compound heterozygous variants c.382G>T: p.(Ala128Ser) and c.2204C>T: p.(Pro735Leu) in TMEM132E were observed in affected but not in unaffected family members. TMEM132E variants identified in this and the previously reported ARNSHI family are located in the extracellular domain. In conclusion, we present a second ARNSHI family with TMEM132E variants which strengthens the evidence of the involvement of this gene in the etiology of ARNSHI.

Background: Greig cephalopolysyndactyly syndrome (GCPS) is a disorder of autopod and craniofacial abnormalities. Autopod anomalies include preaxial and/or postaxial polydactyly together with or without syndactyly while craniofacial features include hypertelorism and macrocephaly. GCPS is inherited in an autosomal dominant manner and is caused by sequence variants in GLI3. Methodology and Results: In this study, we examined four unrelated families with GCPS segregating in an autosomal dominant manner. Sanger sequencing revealed three novel (p.Tyr146Leufs*19, p.Glu99Serfs*60, and p.Thr541Arg) and one previously reported non-sense variant (p.Arg792*) in GLI3. Conclusion: The study expands the spectrum of the variants in the GLI3 gene linked to GCPS, and should also facilitate genetic counseling of GCPS patients in the Pakistani population.