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A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre‐axial polydactyly, post‐axial polydactyly, and syndactyly
Author(s) -
VanderMeer Julia E.,
Afzal Muhammad,
Alyas Saadia,
Haque Sayedul,
Ahituv Nadav,
Malik Sajid
Publication year - 2012
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.35473
Subject(s) - polydactyly , syndactyly , clinodactyly , sonic hedgehog , zone of polarizing activity , limb development , genetics , thumb , hypoplasia , apical ectodermal ridge , biology , anatomy , gene , embryonic stem cell , mesoderm
Limb malformations are one of the most common types of human congenital malformations. Mutations in the ZRS enhancer of Sonic Hedgehog are thought to be responsible for pre‐axial polydactyly in multiple independent families. Here, we describe a large Balochi tribal family from Southern Punjab, Pakistan, with a variable set of limb malformations and a novel ZRS mutation. The family has a limb phenotype characterized by triphalangeal thumb, pre‐axial polydactyly, and post‐axial polydactyly. There is also a high degree of phenotypic heterogeneity with less common clinical findings in the affected family members that include osseous syndactyly of forth–fifth fingers, clinodactyly, hypoplasia of mesoaxial fingers, and bifid halluces. The presentation in most of the affected patients was bilateral and symmetrical. A heterozygous C>A mutation at position 287 of the ZRS enhancer (chr7:156,584,283; hg19) was detected in all affected subjects and is absent from four unaffected family members, 42 unrelated samples, and multiple databases of human variation. Combined, these results identify a novel ZRS287 C>A mutation which leads to a variable spectrum of limb phenotypes. © 2012 Wiley Periodicals, Inc.