[Early prenatal diagnosis for a family affected with X-linked spondyloepiphyseal dysplasia tarda family].
OBJECTIVE
X-linked spondyloepiphyseal dysplasia tarda (SEDL) is a rare osteochondrodysplasia caused by mutations of SEDL gene, which usually onset in late childhood without systemic complications. In this study, we have provided prenatal diagnosis for an affected family with a combined strategy including direct sequencing, fetal-sex identification and microsatellite linkage analysis.


METHODS
Two amniotic fluid samples from carrier gravida and 7 blood samples from individuals in this SEDL pedigree were obtained. Genomic DNA was extracted from the samples using standard phenol-chloroform method. SRY and AMEL genes were employed to assess fetal sex. Microsatellite DXS16 was genotyped for linkage analysis. A pathogenic mutation of the SEDL gene was identified by bi-directionally direct sequencing of the third exon as well as its exon/intron boundaries.


RESULTS
Two male fetuses were confirmed by fetal-sex assessment. The mutation of the SEDL gene was identified as a nucleotide substitution of the splice acceptor site in intron 2, IVS2-2A>C. DNA sequencing indicated that one fetus is hemizygote carrying the mutation, whilst another is not a carrier. Linkage analysis was identical with the sequencing results. Follow-up also confirmed the result of prenatal diagnosis.


CONCLUSIONS
Fetal-sex assessment combined with microsatellite linkage analysis and bi-directionally direct sequencing is a more accurate and ready strategy for prenatal diagnosis of families affected with SEDL.
Rehabilitation Center, Zhengzhou Children's Hospital, Zhengzhou, Henan 450053, P. R. China. kongxd@263.net.
Chao
C
Gao
Huaili
H
Wang
Xiangdong
X
Kong
Qing
Q
Shang
Jiali
J
Duan
Qiang
Q
Luo
D040181:Genetic Diseases, X-Linked / Q000175:diagnosis*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D010009:Osteochondrodysplasias / Q000175:diagnosis*; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA