Recurrent mutations in functionally-related EDA and EDAR genes underlie X-linked isolated hypodontia and autosomal recessive hypohidrotic ectodermal dysplasia.
Mutations in three functionally related genes EDA, EDAR and EDARDD have been reported to cause hypohidrotic ectodermal dysplasia (HED), which is characterized by sparse hair, reduced ability to sweat, and hypodontia. In few cases mutations in the EDA gene have been found to result in X-linked recessive isolated hypodontia. In the study, presented here, we have ascertained two large Pakistani families (A and B) with autosomal recessive form of hypohidrotic ectodermal dysplasia and X-linked recessive isolated hypodontia. Genetic mapping showed linkage of family A to EDAR gene on chromosome 2q11-q13 and family B to EDA gene on chromosome Xq12-q13.1. Subsequently, DNA sequencing of the coding regions of EDAR and EDA genes revealed previously described mutations. Sequence analysis identified a four base-pair splice-junction deletion mutation (c.718_721delAAAG) in EDAR gene in family A and a missense mutation (c.T1091C; p.M364T) in EDA gene in family B. Recurrence of mutations in EDAR and EDA genes in unrelated families is evocative of the dispersion of ancestral chromosome in different locality groups through common ancestors.
Azeem
Zahid
Z
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Naqvi
Syed Kamran-Ul-Hassan
SK
Ansar
Muhammad
M
Wali
Abdul
A
Naveed
Abdul Khaliq
AK
Ali
Ghazanfar
G
Hassan
Muhammad Jawad
MJ
Tariq
Muhammad
M
Basit
Sulman
S
Ahmad
Wasim
W
D000848:Anodontia / Q000235:genetics*; D053360:Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D012008:Recurrence
C506018:EDA protein, human; C506008:EDAR protein, human; D053331:Ectodysplasins; D053339:Edar Receptor