title: Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestations of langer mesomelic dysplasia.
abstract: Haploinsufficiency of SHOX on the short arm pseudoautosomal region (PAR1) leads to Leri-Weill dyschondrosteosis (LWD), and nullizygosity of SHOX results in Langer mesomelic dysplasia (LMD). Molecular defects of LWD/LMD include various microdeletions in PAR1 that involve exons and/or the putative upstream or downstream enhancer regions of SHOX, as well as several intragenic mutations. Here, we report on a Japanese male infant with mild manifestations of LMD and hitherto unreported microdeletions in PAR1. Clinical analysis revealed mesomelic short stature with various radiological findings indicative of LMD. Molecular analyses identified compound heterozygous deletions, that is, a maternally inherited ∼46 kb deletion involving the upstream region and exons 1-5 of SHOX, and a paternally inherited ∼500 kb deletion started from a position ∼300 kb downstream from SHOX. In silico analysis revealed that the downstream deletion did not affect the known putative enhancer regions of SHOX, although it encompassed several non-coding elements which were well conserved among various species with SHOX orthologs. These results provide the possibility of the presence of a novel enhancer for SHOX in the genomic region ∼300 to ∼800 kb downstream of the start codon.
authors: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan; Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors: Takayoshi
authors: T
authors: Tsuchiya
authors: Minoru
authors: M
authors: Shibata
authors: Hironao
authors: H
authors: Numabe
authors: Tomoko
authors: T
authors: Jinno
authors: Kazuhiko
authors: K
authors: Nakabayashi
authors: Gen
authors: G
authors: Nishimura
authors: Toshiro
authors: T
authors: Nagai
authors: Tsutomu
authors: T
authors: Ogata
authors: Maki
authors: M
authors: Fukami
mesh_terms: D001842:Bone and Bones / Q000002:abnormalities / Q000000981:diagnostic imaging; D055028:Comparative Genomic Hybridization; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics*; D057895:Haploinsufficiency; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D017384:Sequence Deletion
keywords: SHOX; deletion; enhancer; langer mesomelic dysplasia