Premium
A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia
Author(s) -
Girisha Katta M.,
Bidchol Abdul Mueed,
Kamath Preeti S.,
Shah Krupa H.,
Mortier Geert R.,
Mundlos Stefan,
Shah Hitesh
Publication year - 2014
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.36367
Subject(s) - zone of polarizing activity , polydactyly , phenotype , genetics , biology , enhancer , mutation , gene , transcription factor , embryonic stem cell , mesoderm
Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH . The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes. © 2014 Wiley Periodicals, Inc.