1. Homozygosity for a novel deletion downstream of theSHOXgene provides evidence for an additional long range regulatory region with a mild phenotypic effect
- Author
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Vivienne Maloney, Moira Blyth, David J. Bunyan, and Emma-Jane Taylor
- Subjects
Adult ,Consanguineous family ,Regulatory Sequences, Nucleic Acid ,Biology ,Osteochondrodysplasias ,Gene Deletions ,Regulatory region ,Consanguinity ,Shox gene ,Short Stature Homeobox Protein ,Genetics ,medicine ,Humans ,Coding region ,Genetic Association Studies ,Growth Disorders ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Aged ,Sequence Deletion ,Homeodomain Proteins ,Comparative Genomic Hybridization ,Langer mesomelic dysplasia ,Point mutation ,Homozygote ,Middle Aged ,medicine.disease ,Phenotype ,Molecular biology ,Pedigree ,Enhancer Elements, Genetic ,Female - Abstract
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.
- Published
- 2014