title: Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss, Pesplanus, Ichthyosis, Cutaneous Nodules, and Keratoderma.
abstract: Mutations in the gap-junction gene Cx30 (Connexin30, GJB6) are a known cause of hearing loss. Here, we report our findings on a large multigeneration family in which severe to profound sensorineural hearing impairment is associated with a variety of skin-related anomalies. Genome-wide analysis of the family showed that the locus maps to chromosome region 13ptel-q12.1 and that a novel mutation, p.N54K, in Cx30, cosegregates with the phenotype. Unlike wild-type Cx30, p.N54K Cx30 is predominantly localized in the cytoplasm and does not permit transfer of neurobiotin, suggesting improper cellular localization and abolishment of gap-junction activity.
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.|Centre for Human Genetics, Bangalore, India.
authors.forename: Nishtha
authors.initials: N
authors.lastname: Pandey
authors.affiliation: Department of Speech and Hearing, School of Allied Health Sciences, Manipal University, Manipal, India.
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Xavier
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Arunima
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Ram-Shankar
authors.initials: RS
authors.lastname: Mani
authors.affiliation: Manipal Hospital, Bangalore, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Hiremagalore
authors.affiliation: Department of Dermatology, Sree Narayana Institute of Medical Sciences, Cochin, India.
authors.forename: Ajith
authors.initials: A
authors.lastname: Tharakan
authors.affiliation: Department of Speech and Hearing, School of Allied Health Sciences, Manipal University, Manipal, India.
authors.forename: B
authors.initials: B
authors.lastname: Rajashekhar
authors.affiliation: Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India.
authors.forename: Anuranjan
authors.initials: A
authors.lastname: Anand
mesh_terms: D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007057:Ichthyosis / Q000235:genetics; D015776:Keratoderma, Palmoplantar, Diffuse / Q000235:genetics; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012873:Skin Diseases, Genetic / Q000235:genetics*
chemical_list: D000075302:Connexin 30; D017630:Connexins; C491020:GJB6 protein, human; C070614:neurobiotin; D001710:Biotin
keywords: Connexin30; cutaneous nodules; gap junction; ichthyosis; neurobiotin; palmoplantar keratoderma; sensorineural hearing loss