A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India.

Abstract

BACKGROUND:

Hypohidrotic/anhidrotic ectodermal dysplasia (HED) is a rare Mendelian disorder affecting ectodermal tissues. The disease is primarily caused by inactivation of any one of three genes, namely ectodysplasin A1 (EDA-A1), which encodes a ligand belonging to the tumour necrosis factor (TNF) superfamily; ectodysplasin A receptor (EDAR), encoding the EDA-A1 receptor and ectodysplasin A receptor-associated death domain (EDARADD), encoding an adaptor protein. X-linked recessive (EDA-A1), the predominant form of HED, as well as autosomal recessive and dominant (EDAR and EDARADD) inheritance patterns have been identified in affected families.

OBJECTIVES:

  To determine the common genes causing HED in India.

METHODS:

 We performed mutation analysis on 26 HED families from India (including 30 patients). In addition, we carried out sequence and structural analysis of missense/nonsense and insertion/deletion mutations.

RESULTS:

Among the 26 families analysed, disease-causing EDAR mutations were identified in 12 (46%) while EDA-A1 mutations were detected in 11 (42%). Four novel mutations in EDAR and five in EDA-A1 were identified. More importantly, a possible founder EDAR mutation, namely c.1144G>A, was identified in five independent families, thus accounting for about one-fifth of affected families in whom mutation was detected. A majority of EDA-A1 mutations localized to the TNF-like domain while the location of EDAR mutations was more widespread.

CONCLUSIONS:

This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.

• Authors: M D Bashyam, A K Chaudhary, E C Reddy, V Reddy, V Acharya, H A Nagarajaram, A R R Devi, L Bashyam, A B Dalal, N Gupta, M Kabra, M Agarwal, S R Phadke, R Tainwala, R Kumar, S V Hariharan
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 166 Issue 4 Pg. 819-29 (Apr 2012) ISSN: 1365-2133 [Electronic] England
• PMID: 22032522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Chemical References

• Receptors, Ectodysplasin

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• DNA Mutational Analysis
• Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive (epidemiology, genetics)
• Exons
• Female
• Founder Effect
• Heterozygote
• Homozygote
• Humans
• India (epidemiology)
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Mutation (genetics)
• Pedigree
• Polymorphism, Single Nucleotide (genetics)
• Receptors, Ectodysplasin (genetics)