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.
Université Paris Descartes, INSERM U, Hôpital Necker-Enfants Malades, France.
Céline
C
Cluzeau
Smail
S
Hadj-Rabia
Marguerite
M
Jambou
Sourour
S
Mansour
Philippe
P
Guigue
Sahben
S
Masmoudi
Elodie
E
Bal
Nicolas
N
Chassaing
Marie-Claire
MC
Vincent
Géraldine
G
Viot
François
F
Clauss
Marie-Cécile
MC
Manière
Steve
S
Toupenay
Martine
M
Le Merrer
Stanislas
S
Lyonnet
Valérie
V
Cormier-Daire
Jeanne
J
Amiel
Laurence
L
Faivre
Yves
Y
de Prost
Arnold
A
Munnich
Jean-Paul
JP
Bonnefont
Christine
C
Bodemer
Asma
A
Smahi
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