X-连锁迟发性脊椎骨骺发育不良SEDL基因新突变

Identification of a novel mutation of the SEDL gene in X-linked spondyloepiphyseal dysplasia tarda

目的 研究X 连锁迟发性脊椎骨骺发育不良 (X linkedspondyloepiphysealdysplasiatarda ,SEDL)的发病机理。方法 应用聚合酶链反应 单链构象多态及变性聚丙烯酰胺测序凝胶电泳技术 ,并结合DNA序列分析方法 ,对 5例SEDL患者及 3 0名正常对照SEDL基因的全部编码外显子及其邻近序列进行突变分析。结果 在 1例SEDL患者中发现了致病突变 ,并经DNA序列分析证实 ,SEDL基因第 5内含子剪接受体处IVS5 2— 1delAG紧接第 6外显子 3 2 2— 3 3 2delTTTTCAATGAA共 13个碱基缺失。结论该突变系国内外尚未见报道的新突变 ,这一突变可引起SEDL。

Objective To investigate further the genetic basis of hereditary X-linked spondyloepiphyseal dysplasia tarda (SEDL). Methods Single strand conformation polymorphism (SSCP) combined with polymerase chain reaction and denaturing polyacrylamide gel electrophoresis were used to detect the mutation for the coding exons of SEDL gene as well as their exon/intron boundaries in 5 unrelated Chinese boys clinically diagnosed as having SEDL. DNA sequencing analysis was further used to identify the mutation. Results The 13 bp deletion mutation consisting of IVS5-2—1delAG and 322—332delTTTTCAATGAA was identified in one of SEDL patients, but not detected in 30 chromosomes from 30 unrelated normal male individuals. Conclusion This is a novel mutation cosegregated with the patient's skeletal disease. The intragenic deletion occurred in the acceptor splice site of the 3′ region of intron 5 and the 5′ coding region of exon 6, which may result in one or a combination of splicing defects. The results of this study expand the spectrum of SEDL mutations associated with SEDL, and this will help to elucidate further the role of this novel protein in the etiology of this form of osteochondrodysplasia.