A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome

TY - JOUR

T1 - A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome

AU - Koppelhus, Uffe

AU - Tranebjaerg, L

AU - Esberg, G

AU - Ramsing, M

AU - Lodahl, M

AU - Rendtorff, N D

AU - Olesen, H V

AU - Sommerlund, Mette

AU - Koppelhus, Uffe

AU - Tranebjaerg, L

AU - Esberg, Gitte

AU - Ramsing, M

AU - Lodahl, Marianne

AU - Rendtorff, Nanna Dahl

AU - Olesen, H V

AU - Sommerlund, Mette

N1 - © The Author(s). CED © 2010 British Association of Dermatologists.

PY - 2011/3/1

Y1 - 2011/3/1

N2 - Background: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder, caused by heterozygous missense mutation in GJB2, encoding the gap junction protein connexin 26. The commonest mutation is the p.Asp50Asn mutation, and only a few other mutations have been described to date. Aim: To report the fatal clinical course and characterize the genetic background of a premature male neonate with the clinical and histological features of KID syndrome. Methods: Genomic DNA was extracted from peripheral blood and used for PCR amplification of the GJB2 gene. Direct sequencing was used for mutation analysis. Results: The clinical features included hearing impairment, ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, alopecia of the scalp and eyelashes, and a thick vernix caseosa-like covering of the scalp. On histological analysis, features characteristic of KID syndrome, such as acanthosis and papillomatosis of the epidermis with basket-weave hyperkeratosis, were seen. The skin symptoms were treated successfully with acitretin 0.5mg/kg. The boy developed intraventricular and intracerebral haemorrhage, leading to hydrocephalus. His condition was further complicated by septicaemia and meningitis caused by infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Severe respiratory failure followed, and the child died at 46weeks of gestational age (13weeks postnatally). Sequencing of the GJB2 gene showed that the child was heterozygous for a novel nucleotide change, c.263C>T, in exon 2, leading to a substitution of alanine for valine at position 88 (p.Ala88Val). Conclusions: This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.

AB - Background: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal disorder, caused by heterozygous missense mutation in GJB2, encoding the gap junction protein connexin 26. The commonest mutation is the p.Asp50Asn mutation, and only a few other mutations have been described to date. Aim: To report the fatal clinical course and characterize the genetic background of a premature male neonate with the clinical and histological features of KID syndrome. Methods: Genomic DNA was extracted from peripheral blood and used for PCR amplification of the GJB2 gene. Direct sequencing was used for mutation analysis. Results: The clinical features included hearing impairment, ichthyosiform erythroderma with hyperkeratotic plaques, palmoplantar keratoderma, alopecia of the scalp and eyelashes, and a thick vernix caseosa-like covering of the scalp. On histological analysis, features characteristic of KID syndrome, such as acanthosis and papillomatosis of the epidermis with basket-weave hyperkeratosis, were seen. The skin symptoms were treated successfully with acitretin 0.5mg/kg. The boy developed intraventricular and intracerebral haemorrhage, leading to hydrocephalus. His condition was further complicated by septicaemia and meningitis caused by infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. Severe respiratory failure followed, and the child died at 46weeks of gestational age (13weeks postnatally). Sequencing of the GJB2 gene showed that the child was heterozygous for a novel nucleotide change, c.263C>T, in exon 2, leading to a substitution of alanine for valine at position 88 (p.Ala88Val). Conclusions: This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.

KW - Animals

KW - Biopsy

KW - Connexins

KW - Deafness

KW - Dermatologic Agents

KW - Fatal Outcome

KW - Humans

KW - Ichthyosis

KW - Infant, Newborn

KW - Infant, Premature

KW - Infant, Premature, Diseases

KW - Keratitis

KW - Male

KW - Mutation

KW - Skin

U2 - 10.1111/j.1365-2230.2010.03936.x

DO - 10.1111/j.1365-2230.2010.03936.x

M3 - Journal article

C2 - 20846357

SN - 0307-6938

VL - 36

SP - 142

EP - 148

JO - Clinical and Experimental Dermatology

JF - Clinical and Experimental Dermatology

IS - 2

ER -