Funding sources The study was supported by a core grant from the Department of Biotechnology, Government of India to the Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India
Article first published online: 5 MAR 2012
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 166, Issue 4, pages 819–829, April 2012
How to Cite
Bashyam, M.D., Chaudhary, A.K., Reddy, E.C., Reddy, V., Acharya, V., Nagarajaram, H.A., Devi, A.R.R., Bashyam, L., Dalal, A.B., Gupta, N., Kabra, M., Agarwal, M., Phadke, S.R., Tainwala, R., Kumar, R. and Hariharan, S.V. (2012), A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India. British Journal of Dermatology, 166: 819–829. doi: 10.1111/j.1365-2133.2011.10707.x
Conflicts of interest All authors declare no conflict of interest.
- Issue published online: 27 MAR 2012
- Article first published online: 5 MAR 2012
- Accepted manuscript online: 27 OCT 2011 03:50PM EST
- Accepted for publication , 20 October 2011
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.