title: Homozygosity for a novel deletion downstream of the SHOX gene provides evidence for an additional long range regulatory region with a mild phenotypic effect.
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.
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, Wiltshire, SP2 8BJ, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bunyan
authors.forename: Emma-Jane
authors.initials: EJ
authors.lastname: Taylor
authors.forename: Vivienne K
authors.initials: VK
authors.lastname: Maloney
authors.forename: Moira
authors.initials: M
authors.lastname: Blyth
mesh_terms: D000328:Adult; D000368:Aged; D055028:Comparative Genomic Hybridization; D003241:Consanguinity; D004742:Enhancer Elements, Genetic; D005260:Female; D056726:Genetic Association Studies; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D000074122:Short Stature Homeobox Protein
chemical_list: D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein
keywords: SHOX; downstream deletion; regulatory element