[Identification of a novel mutation IVS2-2A-->C of SEDL gene in a Chinese family with X-linked spondyloepiphyseal dysplasia tarda].
OBJECTIVE
To identify the mutation of spondyloepiphyseal dysplasia tarda (SEDL) gene in a large Chinese family with X-linked spondyloepiphyseal dysplasia tarda and to make a discussion on the pathogenesis of SEDL at the molecular level.


METHODS
In two patients, four exons comprising the SEDL open reading frame as well as their exon/intron boundaries were analyzed by bi-directional direct sequencing of PCR products. The sequencing results were compared against the normal sequences in GenBank to find the mutation. Then the mutation was identified in other members of the family.


RESULTS
A nucleotide substitution of the splice acceptor in SEDL intron 2, IVS2 -2A-->C,was detected in two affected individuals (IV(15)  V(3)) in the Chinese family with SEDL, but no sequence change occurring on exons 3-6 was detected. The transversion was also identified in four heterozygous carriers. The mutation was not found in two unaffected male individuals and fifteen normal controls. Furthermore, four potential carriers were identified in the family.


CONCLUSIONS
The mutation IVS2 -2A-->C of SEDL gene was firstly determined in the world. The change of the splice acceptor in SEDL intron 2 may cause skipping of exon 3  which is responsible for the disease. Molecular diagnosis can be made by detecting the mutation.
Gao
Chao
C
Paediatric Department of the First Affiliated Hospital, Zhengzhou University, Henan, PR China. gaochao39@371.net
Luo
Qiang
Q
Wang
Huai-li
HL
Gao
Xiao-qun
XQ
Fan
Qing-tang
QT
Wang
Hua
H
Sheng
Guang-yao
GY
Zhou
Jian-hua
JH
Gao
Tie-zheng
TZ
D017398:Alternative Splicing / Q000235:genetics; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002681:China; D041321:Chromosomes, Human, X / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D014157:Transcription Factors
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C120759:TRAPPC2 protein, human; D014157:Transcription Factors; D004247:DNA