A novel insertion mutation in the SEDL gene results in X-linked spondyloepiphyseal dysplasia tarda in a large Chinese pedigree.
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.
Xia
Xin-Yi
XY
Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, PR China.
Cui
Ying-Xia
YX
Zhou
Yu-Chun
YC
Zhou
Xin
X
Shi
Yi-Chao
YC
Wei
Li
L
Li
Xiao-Jun
XJ
Huang
Yu-Feng
YF
Huang
Ting-Ting
TT
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*
D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C120759:TRAPPC2 protein, human; D014157:Transcription Factors