title: WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes.
abstract: Odonto-onycho-dermal dysplasia (OODD), a rare autosomal-recessive inherited form of ectodermal dysplasia including severe oligodontia, nail dystrophy, palmoplantar hyperkeratosis, and hyperhidrosis, was recently shown to be caused by a homozygous nonsense WNT10A mutation in three consanguineous Lebanese families. Here, we report on 12 patients, from 11 unrelated families, with ectodermal dysplasia caused by five previously undescribed WNT10A mutations. In this study, we show that (1) WNT10A mutations cause not only OODD but also other forms of ectodermal dysplasia, reaching from apparently monosymptomatic severe oligodontia to Schöpf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors; (2) WNT10A mutations are a frequent cause of ectodermal dysplasia and were found in about 9% of an unselected patient cohort; (3) about half of the heterozygotes (53.8%) show a phenotype manifestation, including mainly tooth and nail anomalies, which was not reported before in OODD; and (4) heterozygotes show a sex-biased manifestation pattern, with a significantly higher proportion of tooth anomalies in males than in females, which may implicate gender-specific differences of WNT10A expression.
authors: Institut für Humangenetik, Westfälische Wilhelms-Universität, 48149 Münster, Germany. abohring@aol.com
authors: Axel
authors: A
authors: Bohring
authors: Thomas
authors: T
authors: Stamm
authors: Christiane
authors: C
authors: Spaich
authors: Claudia
authors: C
authors: Haase
authors: Kerstin
authors: K
authors: Spree
authors: Ute
authors: U
authors: Hehr
authors: Mandy
authors: M
authors: Hoffmann
authors: Susanne
authors: S
authors: Ledig
authors: Saadettin
authors: S
authors: Sel
authors: Peter
authors: P
authors: Wieacker
authors: Albrecht
authors: A
authors: Röpke
mesh_terms: D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012727:Sex Characteristics; D051153:Wnt Proteins / Q000235:genetics*
chemical_list: C484142:WNT10A protein, human; D051153:Wnt Proteins