title: Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes.
abstract: Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose а KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (сonnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease.
authors.affiliation: Department the Epidemiology and Genetics of Hearing Loss, National Research Center for Audiology and Hearing Rehabilitation, 123 Leninsky Ave, 117513 Moscow, Russia. Electronic address: tmarkova@audiology.ru.
authors.forename: T G
authors.initials: TG
authors.lastname: Markova
authors.affiliation: Out-Patient Clinic, National Research Center for Audiology and Hearing Rehabilitation, 123 Leninsky Ave, 117513 Moscow, Russia.
authors.forename: N B
authors.initials: NB
authors.lastname: Brazhkina
authors.affiliation: Laboratory for DNA-Diagnostics, Federal State Budgetary Institution "Research Centre for Medical Genetics", 1, Room 116 Moskvorechie Str, 115478 Moscow, Russia. Electronic address: bliznetzelena@mail.ru.
authors.forename: E A
authors.initials: EA
authors.lastname: Bliznech
authors.affiliation: Cochlear Implants Center, National Research Center for Audiology and Hearing Rehabilitation, 123 Leninsky Ave, 117513 Moscow, Russia. Electronic address: bakhshinyan@yahoo.com.
authors.forename: V V
authors.initials: VV
authors.lastname: Bakhshinyan
authors.affiliation: Laboratory for DNA-Diagnostics, Federal State Budgetary Institution "Research Centre for Medical Genetics", 1, Room 116 Moskvorechie Str, 115478 Moscow, Russia. Electronic address: apol@dnalab.ru.
authors.forename: A V
authors.initials: AV
authors.lastname: Polyakov
authors.affiliation: National Research Center for Audiology and Hearing Rehabilitation, 123 Leninsky Ave, 117513 Moscow, Russia. Electronic address: gtavartkiladze@audiology.ru.
authors.forename: G A
authors.initials: GA
authors.lastname: Tavartkiladze
mesh_terms: D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003937:Diagnosis, Differential; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007634:Keratitis / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Clouston syndrome; Connexin26; GJB2 and GJB6 gene mutation; Hereditary hearing loss; Keratitis–ichthyosis–deafness syndrome