一个X连锁隐性遗传性脑积水家系L1CAM基因的突变分析

Analysis of L1CAM gene mutation in pedigrees with X-linked genetic hydrocephalus

目的 分析一个X连锁隐性遗传性脑积水家系中L1CAM基因的变异,并为其提供产前诊断.方法 该夫妇先后3次在妊娠22周左右经B超发现胎儿脑积水,且引产儿均为男性.提取其第3次妊娠流产物的DNA,首先进行叶酸代谢能力基因检测和染色体微阵列分析,之后进行高通量测序.用Sanger测序对疑似突变进行验证.结果 胎儿叶酸代谢能力基因(MTHFR C677T)以及染色体微阵列分析均未见异常,但携带L1CAM基因的c.512G>A(p.Trp171Ter)半合子变异,后者遗传自表型正常的母亲.该变异为新变异,具有致病性.结论 L1CAM基因的c.512G>A(p.Trp171Ter)变异很可能是该家系的致病变异.对于反复孕育男性脑积水胎儿的夫妇,可对其进行L1CAM基因的变异筛查.

Objective To analyze L1CAM gene mutation in a family featuring X-linked recurrent fetal hydrocephalus.Methods The family had three pregnancies where a male fetus was detected at 22 weeks with hydrocephalus by ultrasonography.DNA was extracted from peripheral blood samples from the parents as well as fetal tissue from the third abortion.The fetal DNA was subjected to testing of folic acid metabolism ability gene and chromosomal microarray analysis(CMA).And next-generation sequencing(NGS)was employed to detect potential mutation of related genes.Suspected mutation was verified by Sanger sequencing.Results Testing of folic acid metabolism ability gene(MTHFR C677T)and CMA were both normal.A c.512G>A(p.Trp171Ter)hemizygous mutation of the L1CAM gene was detected in the fetal tissue,which is inherited from the phenotypically normal mother.The novel mutation was predicted to be pathogenic.Conclusion The c.512G>A(p.Trp171Ter)mutation of the L1CAM gene probably underlies the X-linked hydrocephalus in this family.Screening of L1CAM gene variations should be carried out for couples experiencing recurrent fetal hydrocephalus affecting the male gender.