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Homozygosity for a novel deletion downstream of the SHOX gene provides evidence for an additional long range regulatory region with a mild phenotypic effect
Author(s) -
Bunyan David J.,
Taylor EmmaJane,
Maloney Vivienne K.,
Blyth Moira
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.36724
Subject(s) - genetics , phenotype , biology , gene , point mutation , coding region , mutation , regulatory sequence , regulation of gene expression
Léri–Weill dyschondrosteosis is caused by heterozygous mutations in SHOX or its flanking sequences, including whole or partial gene deletions, point mutations within the coding sequence, and deletions of downstream regulatory elements. The same mutations when biallelic cause the more severe Langer Mesomelic dysplasia. Here, we report on a consanguineous family with a novel deletion downstream of SHOX in which homozygously deleted individuals have a phenotype intermediate between Léri–Weill dyschondrosteosis and Langer Mesomelic dysplasia while heterozygously deleted individuals are mostly asymptomatic. The deleted region is distal to all previously described 3′ deletions, suggesting the presence of an additional regulatory element, deletions of which have a milder, variable phenotypic effect. © 2014 Wiley Periodicals, Inc.