Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases.
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, (1) EDA1 accounting for X-linked forms, (2) EDAR, and (3) 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: (1) the EDA1 gene was the most common disease-causing gene (58% of cases), (2)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. Although 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.
Cluzeau
Céline
C
Université Paris Descartes, INSERM U, Hôpital Necker-Enfants Malades, France.
Hadj-Rabia
Smail
S
Jambou
Marguerite
M
Mansour
Sourour
S
Guigue
Philippe
P
Masmoudi
Sahben
S
Bal
Elodie
E
Chassaing
Nicolas
N
Vincent
Marie-Claire
MC
Viot
Géraldine
G
Clauss
François
F
Manière
Marie-Cécile
MC
Toupenay
Steve
S
Le Merrer
Martine
M
Lyonnet
Stanislas
S
Cormier-Daire
Valérie
V
Amiel
Jeanne
J
Faivre
Laurence
L
de Prost
Yves
Y
Munnich
Arnold
A
Bonnefont
Jean-Paul
JP
Bodemer
Christine
C
Smahi
Asma
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004476:Ectodermal Dysplasia / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D053339:Edar Receptor / Q000235:genetics*; D053362:Edar-Associated Death Domain Protein / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D051153:Wnt Proteins / Q000235:genetics*; D055815:Young Adult
C506018:EDA protein, human; C506008:EDAR protein, human; C506125:EDARADD protein, human; D053331:Ectodysplasins; D053339:Edar Receptor; D053362:Edar-Associated Death Domain Protein; C484142:WNT10A protein, human; D051153:Wnt Proteins