Duplications upstream and downstream of SHOX identified as novel causes of Leri-Weill dyschondrosteosis or idiopathic short stature

Leri–Weill dyschondrosteosis is a pseudoautosomal dominantly‐inherited skeletal dysplasia ascribed to haploinsufficiency of the SHOX gene caused by deletions, point mutations, or partial duplications of the gene, or to heterozygous deletions upstream or downstream of the intact SHOX gene involving c...

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Vydáno v:	American journal of medical genetics. Part A Ročník 170A; číslo 4; s. 949 - 957
Hlavní autoři:	Bunyan, David J., Baffico, Maria, Capone, Lucia, Vannelli, Silvia, Iughetti, Lorenzo, Schmitt, Sébastien, Taylor, Emma-Jane, Herridge, Adam A., Shears, Deborah, Forabosco, Antonino, Coviello, Domenico A.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Blackwell Publishing Ltd 01.04.2016 Wiley Subscription Services, Inc
Témata:	Adolescent Adult Bone dysplasia Child Child, Preschool Chromosome Duplication Cohort Studies Comparative Genomic Hybridization Deoxyribonucleic acid DNA Duplication Dwarfism - diagnosis Dwarfism - genetics Female Genomes Growth Disorders - diagnosis Growth Disorders - genetics Haploinsufficiency Haplotypes Homeodomain Proteins - genetics Humans Hybridization Male Mutation Osteochondrodysplasias - diagnosis Osteochondrodysplasias - genetics Pedigree Phenotype Regulatory element Short Stature Homeobox Protein SHOX Skeleton Young Adult Duplication SHOX Regulatory element
ISSN:	1552-4825, 1552-4833, 1552-4833
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Popis
Shrnutí:	Leri–Weill dyschondrosteosis is a pseudoautosomal dominantly‐inherited skeletal dysplasia ascribed to haploinsufficiency of the SHOX gene caused by deletions, point mutations, or partial duplications of the gene, or to heterozygous deletions upstream or downstream of the intact SHOX gene involving conserved non‐coding cis‐regulatory DNA elements that show enhancer activity. Recently, two SHOX conserved non‐coding element duplications, one upstream and one downstream, were reported in patients referred with idiopathic short stature. To further evaluate the role of these duplications in SHOX‐related disorders, we describe seven patients (five with Leri‐Weill dyschondrosteosis and two with short stature) all of whom have duplications of part of the upstream or downstream conserved non‐coding element regions, identified by multiplex ligation‐dependent probe amplification. In addition, we show data from 32 patients with an apparently identical downstream duplication that includes a proposed putative regulatory element (identified by multiplex ligation‐dependent probe amplification or array comparative genome hybridization), which results in a variable phenotype from normal to mild Leri–Weill dyschondrosteosis. These additional data provide further evidence that duplications of upstream and downstream long range cis‐regulatory DNA elements can result in a SHOX‐related phenotype. © 2015 Wiley Periodicals, Inc.
Bibliografie:	ArticleID:AJMGA37524 istex:7ACE703ABE9BF31DA00FD59312F5EC1495226994 Italian Telethon - No. GTB12001 ark:/67375/WNG-TQ0C183N-3 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1552-4825 1552-4833 1552-4833
DOI:	10.1002/ajmg.a.37524