title: A novel splicing mutation in the SEDL gene causes spondyloepiphyseal dysplasia tarda in a large Chinese pedigree.
abstract: The X-linked form of spondyloepiphyseal dysplasia tarda (SEDT, OMIM# 313400) is a rare osteochondrodysplasia caused by mutations in the SEDL (TRAPPC2, OMIM# 300202) gene. It is clinically characterized by disproportionate short stature, barrel-shaped chests and early development of degenerative joint disease. We report here a novel mutation in the intron 3 splice-donor site (c. 93+5G>C) segregated in an X-link pattern in a large Chinese family with SEDT. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the mutation causes an aberrant splicing of exon 3, resulting in the elimination of 31 codons in the exon and a considerable loss function of the SEDL protein. This mutation was not detected in the 100 healthy controls. This novel mutation adds to the spectrum of previously-identified disease-causing mutations. Pre-symptomatic molecular diagnosis and prenatal diagnosis of the pregnant carriers could be helpful to families with SEDT.
authors.affiliation: Prenatal Diagnosis Center, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xu
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
mesh_terms: D044466:Asian People; D001483:Base Sequence; D016022:Case-Control Studies; D041321:Chromosomes, Human, X; D003062:Codon; D005091:Exons; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007438:Introns; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D011247:Pregnancy; D022821:RNA Splice Sites; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D003062:Codon; D026901:Membrane Transport Proteins; D022821:RNA Splice Sites; C120759:TRAPPC2 protein, human; D014157:Transcription Factors
keywords: SEDL gene; Splicing mechanism; Splicing mutation; Spondyloepiphyseal dysplasia tarda (SEDT); X-linked