一个常染色体显性智力低下1型家系的MBD5基因新变异

目的对1例智力、运动发育落后、语言发育严重受损、面部畸形合并癫痫的患儿及其家系成员进行基因变异分析。方法应用全外显子分析技术对先证者进行致病变异筛查,结合先证者的表型确定候选致病位点,应用Sanger测序对先证者、父母及其他家系成员进行变异位点验证。结果先证者携带MBD5基因c.2217delT(p.F739Lfs*6)框移变异,文献未见报道,来源于母亲,经家系验证,其兄携带相同变异且具有相似的表型,其母年幼时语言表达能力差,学习成绩差,可做家务,无抽搐病史。结论发现一个MBD5基因新的致病变异,丰富了MBD5基因变异谱,家系研究发现该基因变异存在表现度差异。本研究结果为该家系的病因诊断和产前诊断提供了依据。

Identification of a novel mutation of MBD5 gene in a pedigree affected with autosomal dominant mental retardation type 1

Objective To explore the genetic basis for a child with mental and motor retardation,language impairment,facial dysmorphism and epilepsy.Methods Whole exome sequencing was carried out to detect pathogenic variant in the proband,and candidate variant was selected based on his phenotype.Sanger sequencing was used to verify the variant in the proband,his parents and other family members.Results The proband was found to carry a frameshifting mutation of MBD5 gene,namely c.2217delT(p.F739Lfs*6),which was inherited from his mother and unreported previously.Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype.His mother also had poor language expression when she was young,in addition with poor academic performance,though she could do some housework and had no history of convulsion.Conclusion A novel pathogenic variant of the MBD5 gene was discovered,which has enriched the mutational spectrum of the MBD5 gene.Above discovery has enabled genetic counseling and prenatal diagnosis for the family.