Julia E VanderMeer and Muhammad Afzal contributed equally to this work.
A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly†
Version of Record online: 11 JUL 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 8, pages 2031–2035, August 2012
How to Cite
VanderMeer, J. E., Afzal, M., Alyas, S., Haque, S., Ahituv, N. and Malik, S. (2012), A novel ZRS mutation in a Balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly. Am. J. Med. Genet., 158A: 2031–2035. doi: 10.1002/ajmg.a.35473
How to Cite this Article: VanderMeer JE, Afzal M, Alyas S, Haque S, Ahituv N, Malik S. 2012. A novel ZRS mutation in a balochi tribal family with triphalangeal thumb, pre-axial polydactyly, post-axial polydactyly, and syndactyly. Am J Med Genet Part A. 158A:2031–2035.
- Issue online: 19 JUL 2012
- Version of Record online: 11 JUL 2012
- Manuscript Accepted: 18 APR 2012
- Manuscript Received: 9 FEB 2012
- NICHD. Grant Number: R01HD059862
- Higher Education Commission Pakistan
- Pakistan Science Foundation
- triphalangeal thumb;
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.