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Al‐Awadi–Raas‐Rothschild (limb/pelvis/uterus–hypoplasia/aplasia) syndrome and WNT7A mutations: Genetic homogeneity and nosological delineation
Author(s) -
Garavelli Livia,
Wischmeijer Anita,
Rosato Simonetta,
Gelmini Chiara,
Reverberi Sandro,
Sassi Silvia,
Ferrari Adriano,
Mari Francesca,
Zabel Bernhard,
Lausch Ekkehart,
Unger Sheila,
SupertiFurga Andrea
Publication year - 2011
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33793
Subject(s) - aplasia , hypoplasia , limb development , phenotype , loss function , genetics , biology , medicine , anatomy , gene
The Al‐Awadi–Raas‐Rothschild syndrome (AARRS; OMIM 276820) and the Fuhrmann syndrome (FS; OMIM 228930) are distinct limb malformation disorders comprising different degrees of limb aplasia or hypoplasia. In 2006, Woods et al. found different recessive WNT7A mutations in one family segregating the AARRS phenotype and in a second family with FS. To explain the common genetic basis for the two clinically distinct disorders, functional studies were done showing that partial loss of WNT7A function resulted in FS, while complete loss of WNT7A function resulted in the more severe phenotype of AARRS. In spite of the elucidation of the molecular basis of AARRS, there remains to this day considerable diagnostic confusion that has culminated in the lumping of Schinzel phocomelia syndrome with AARRS; however, this phocomelic limb defect is quite different in its clinical aspect and pathogenesis from the limb findings of AARRS. Here, we report on a child with the AARRS phenotype and homozygosity for a non‐conservative E72K mutation in WNT7A , underline the homogeneity of the WNT7A ‐associated AARRS phenotype, and propose differential diagnostic criteria for the AARRS reflecting the roles of WNT7A in limb development. © 2010 Wiley‐Liss, Inc.