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

Uffe Koppelhus; L Tranebjaerg; G Esberg; M Ramsing; M Lodahl; N D Rendtorff; H V Olesen; Mette Sommerlund; Uffe Koppelhus; L Tranebjaerg; Gitte Esberg; M Ramsing; Marianne Lodahl; Nanna Dahl Rendtorff; H V Olesen; Mette Sommerlund

doi:10.1111/j.1365-2230.2010.03936.x

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

Uffe Koppelhus, L Tranebjaerg, G Esberg, M Ramsing, M Lodahl, N D Rendtorff, H V Olesen, Mette Sommerlund, Uffe Koppelhus, L Tranebjaerg, Gitte Esberg, M Ramsing, Marianne Lodahl, Nanna Dahl Rendtorff, H V Olesen, Mette Sommerlund

Medical Genetics Program

31 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Clinical and Experimental Dermatology
Vol/bind	36
Udgave nummer	2
Sider (fra-til)	142-8
Antal sider	7
ISSN	0307-6938
DOI	https://doi.org/10.1111/j.1365-2230.2010.03936.x
Status	Udgivet - 1 mar. 2011

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10.1111/j.1365-2230.2010.03936.x

Citationsformater

Koppelhus, U., Tranebjaerg, L., Esberg, G., Ramsing, M., Lodahl, M., Rendtorff, N. D., Olesen, H. V., Sommerlund, M., Koppelhus, U., Tranebjaerg, L., Esberg, G., Ramsing, M., Lodahl, M., Rendtorff, N. D., Olesen, H. V., & Sommerlund, M. (2011). A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome. Clinical and Experimental Dermatology, 36(2), 142-8. https://doi.org/10.1111/j.1365-2230.2010.03936.x

Koppelhus, U, Tranebjaerg, L, Esberg, G, Ramsing, M, Lodahl, M, Rendtorff, ND, Olesen, HV, Sommerlund, M, Koppelhus, U, Tranebjaerg, L, Esberg, G, Ramsing, M, Lodahl, M, Rendtorff, ND, Olesen, HV & Sommerlund, M 2011, 'A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome', Clinical and Experimental Dermatology, bind 36, nr. 2, s. 142-8. https://doi.org/10.1111/j.1365-2230.2010.03936.x

@article{10f48240e4be4bb9a3531bf4ced9e358,

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

abstract = "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.",

keywords = "Animals, Biopsy, Connexins, Deafness, Dermatologic Agents, Fatal Outcome, Humans, Ichthyosis, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Keratitis, Male, Mutation, Skin",

author = "Uffe Koppelhus and L Tranebjaerg and G Esberg and M Ramsing and M Lodahl and Rendtorff, {N D} and Olesen, {H V} and Mette Sommerlund and Uffe Koppelhus and L Tranebjaerg and Gitte Esberg and M Ramsing and Marianne Lodahl and Rendtorff, {Nanna Dahl} and Olesen, {H V} and Mette Sommerlund",

note = "{\textcopyright} The Author(s). CED {\textcopyright} 2010 British Association of Dermatologists.",

year = "2011",

month = mar,

day = "1",

doi = "10.1111/j.1365-2230.2010.03936.x",

language = "English",

volume = "36",

pages = "142--8",

journal = "Clinical and Experimental Dermatology",

issn = "0307-6938",

publisher = "Wiley-Blackwell",

number = "2",

}

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

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 -

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

Abstract

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