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Ectrodactyly with aplasia of long bones (OMIM; 119100) in a large inbred Arab family with an apparent autosomal dominant inheritance and reduced penetrance: Clinical and genetic analysis
Author(s) -
Naveed Mohammed,
AlAli Mahmoud T.,
Murthy Sabita K.,
AlHajali Sarah,
AlKhaja Najib,
Deutsch Samuel,
Bottani Armand,
Antonarakis Stylianos E.,
Nath Swapan K.,
Radhakrishna Uppala
Publication year - 2006
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.31239
Subject(s) - ectrodactyly , penetrance , polydactyly , aplasia , syndactyly , haplotype , genetics , variable expression , medicine , allele , biology , ectodermal dysplasia , anatomy , phenotype , gene
Ectrodactyly with aplasia of long bones syndrome is one of the most recognizable defects involving the extremities. We have studied a very large eight‐generation consanguineous Arab family from the United Arab Emirates (UAE) with multiple severe limb anomalies resembling this condition (OMIM; 119100), for which the affected gene is unknown. The pedigree consists of 145 individuals including 23 affected (14 males/9 females) with limb anomalies. Of these, 18 had tibial aplasia (TA) usually on the right side. The expression of the phenotype was variable and ranged from bilateral to unilateral TA with ectrodactyly and other defects of the extremities. The mode of inheritance appears to be autosomal dominant with reduced penetrance. There were 10 consanguineous marriages observed in this pedigree. This could suggest possible pseudodominance due to high frequency of the mutant allele. Candidate loci for the described syndrome include GLI3 (OMIM: 165240) on 7p13, sonic hedgehog; (OMIM: 600725) on 7q36, Langer–Giedion syndrome (OMIM: 150230) on 8q24.1 and split‐hand/foot malformation 3 (OMIM: 600095) on 10q24. In addition, bilateral tibial hemimelia and unilateral absence of the ulna was previously observed to co‐segregate with deletion of 8q24.1. Two‐point linkage and haplotype analyses did not show the involvement of the above regions in this family. © 2006 Wiley‐Liss, Inc.