title: A novel insertion mutation in the SEDL gene results in X-linked spondyloepiphyseal dysplasia tarda in a large Chinese pedigree.
abstract: BACKGROUND
  Spondyloepiphyseal dysplasia tarda (SEDT) is an X-chromosome linked primary skeletal dysplasia characterized by a disproportionate short-trunked short stature, dysplasia of the large joints and flattened thoracic and lumber vertebral bodies. The objective of this study is to describe a large Chinese SEDT family with a milder phenotype and describe the molecular and clinical findings.
  
  
  METHODS
  Eight affected males of the family were diagnosed with SEDT according to their clinical and radiological features. Direct DNA sequencing of the SEDL gene was performed. RT-PCR experiments on total RNA from blood lymphocytes were performed to confirm the defect on the SEDL gene. A short summary of all currently known SEDL gene mutations is presented.
  
  
  RESULTS
  DNA sequencing revealed that all the affected males carried an insertion mutation (c.370-371insA) unreported previously, predicted to result in frameshifts and generate a premature stop codon (p.S124fsX127). The identical mutation was also observed in a 10-year old presymptomatic boy of the family. Eight female carriers had the typical sequencing chromatograms of heterozygotes.
  
  
  CONCLUSIONS
  Identification of the novel insertion mutation (c.370-371insA) in this SEDT family enables carrier detection and presymptomatic/prenatal diagnosis, but also the detailed molecular and clinical features will be useful for extending the evidence for genetic and phenotypic heterogeneity in SEDT.
authors.affiliation: Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, PR China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Xia
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Cui
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Huang
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
mesh_terms: D001483:Base Sequence; D002681:China; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C120759:TRAPPC2 protein, human; D014157:Transcription Factors