Premium
A novel missense mutation in the ectodysplasin‐A ( EDA ) gene underlies X‐linked recessive nonsyndromic hypodontia
Author(s) -
Ayub Muhammad,
UrRehman Fazal,
Yasinzai Masoom,
Ahmad Wasim
Publication year - 2010
Publication title -
international journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 93
eISSN - 1365-4632
pISSN - 0011-9059
DOI - 10.1111/j.1365-4632.2010.04596.x
Subject(s) - hypohidrotic ectodermal dysplasia , hypodontia , genetics , missense mutation , axin2 , biology , locus (genetics) , anodontia , exon , oligodontia , mutation , gene , medicine , wnt signaling pathway , dentistry , orthodontics
Background Nonsyndromic hypodontia or congential absence of one or more permanent teeth is a common anomaly of dental development in humans. This condition may be inherited in an autosomal (dominant/recessive) or X‐linked (dominant/recessive) mode. Mutations in three genes, PAX9 , MSX1 , and AXIN2 , have been determined to be associated with autosomal dominant and recessive tooth agenesis. Recent studies in a few families showed that mutations in the ectodysplasin A ( EDA ) gene result in X‐linked nonsyndromic hypodontia. Methods Genotyping of a five‐generation Pakistani family with X‐linked isolated hypodontia having three affected men was carried out using EDA‐linked polymorphic microsatellite markers on chromosome Xq12‐q13.1. To screen for a mutation in the EDA gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer. Results We successfully mapped the affected locus to chromosome Xq12‐q13.1, and found a novel missense mutation (c.993G>C) in the EDA gene in the affected men. The mutation causes substitution of glutamine with histidine (p.Q331H) in the tumor necrosis factor homology domain of EDA . Conclusions A mutation identified in this study extends the body of evidence implicating the EDA gene in X‐linked nonsyndromic hypodontia and supports the role of EDA‐EDAR‐EDARADD signaling in the morphogenesis of teeth.