Only four genes (EDA1, EDAR, EDARADD and WNT10A) account for 90 % of hypohidrotic/anhidrotic ectodermal dysplasia cases

Céline Cluzeau (1) , Smail Hadj-Rabia (1, 2) , Marguerite Jambou (3) , Sourour Mansour (1) , Philippe Guigue (1) , Sahben Masmoudi (3) , Elodie Bal (1) , Nicolas Chassaing (4) , Marie-Claire Vincent (5) , Geraldine Viot (6) , François Clauss (7, 8) , Marie-Cécile Manière (7) , Steve Toupenay (9) , Martine Le Merrer (1) , Stanislas Lyonnet (1) , Valerie Cormier-Daire (1) , Jeanne Amiel (1) , Laurence Faivre (10) , Yves de Prost (1) , Arnold Munnich (1) , Jean-Paul Bonnefont (1, 3) , Christine Bodemer (1, 11) , Asma Smahi (1)

1 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
2 Centre de Référence National des Maladies Génétiques à Expression Cutanée (MAGEC), Service de Dermatologie
3 Service de Génétique Médicale [CHU Necker]
4 CPTP - Centre de Physiopathologie Toulouse Purpan
5 Nouvel Hôpital Civil de Strasbourg
6 Maternité Port-Royal [CHU Cochin]
7 Hôpitaux universitaires
8 Biomatériaux et ingénierie tissulaire
9 Hôpital de l'Hôtel Dieu
10 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
11 Service de dermatologie pédiatrique

Hypohidrotic and anhidrotic ectodermal dysplasia (HED/EDA) is a rare genodermatosis characterized by abnormal development of sweat glands, teeth and hair. Three disease causing genes have been hitherto identified, namely i) EDA1 accounting for X-linked forms, ii) EDAR, and iii) EDARADD, causing both autosomal dominant and recessive forms. Recently, WNT10A gene was identified as responsible for various autosomal recessive forms of ectodermal dysplasias, including onycho-odonto-dermal dysplasia (OODD) and Schöpf-Schulz-Passarge syndrome. We systematically studied EDA1, EDAR, EDARADD and WNT10A genes in a large cohort of 65 unrelated patients, of which 61 presented with HED/EDA. A total of 50 mutations (including 32 novel mutations) accounted for 60/65 cases in our series. These four genes accounted for 92 % (56/61 patients) of HED/EDA cases: i) EDA1 gene was the most common disease causing gene (58 % of cases), ii) WNT10A and EDAR were each responsible for 16 % of cases. Moreover, a novel disease locus for dominant HED/EDA mapped to chromosome 14q12-q13.1. While no clinical differences between patients carrying EDA1, EDAR or EDARADD mutations could be identified, patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism), helping to decide which gene should be first investigated in HED/EDA.

Mots clés: Life Sciences

Domaines: Médecine humaine et pathologie

Céline Cluzeau, Smail Hadj-Rabia, Marguerite Jambou, Sourour Mansour, Philippe Guigue, et al.. Only four genes (EDA1, EDAR, EDARADD and WNT10A) account for 90 % of hypohidrotic/anhidrotic ectodermal dysplasia cases. Human Mutation, 2010, 32 (1), pp.70. ⟨10.1002/humu.21384⟩. ⟨hal-00599475⟩