一例Adams-Oliver综合征2型患儿的DOCK6基因变异分析

Analysis of DOCK6 gene mutation in a child affected with Adams-Oliver syndrome type 2

目的对1例惊厥发作、临床诊断为难治性癫痫的患儿进行DOCK6基因变异分析,明确其遗传学病因。方法应用染色体微阵列分析和新一代测序技术,对该家系进行分子遗传学分析。结果测序结果显示患儿DOCK6基因(NM_020812.3)存在c.188C>T(p.Arg63Gln)和c.5374C>T(p.Glu1792Lys)复合杂合变异,患儿父亲携带c.5374C>T杂合变异,母亲携带c.188C>T杂合变异,表明患儿的2个变异分别来自母亲和父亲,均为未报道过的新变异。两个位点在多个物种中均高度保守,按照美国医学遗传学学会指南,c.5374C>T变异为疑似致病变异,c.188C>T变异为临床意义未明。结论DOCK6基因c.188C>T(p.Arg63Gln)和c.5374C>T(p.Glu1792Lys)复合杂合变异可能为患儿的致病原因,新变异的检出丰富了DOCK6基因突变谱。

Objective To detect pathogenic mutation of DOCK6 gene in a patient with convulsive seizure and refractory epilepsy. Methods CytoScan HD-Array and next generation sequencing were used to detect the potential mutation in the patient. Results The proband has carried compound heterozygous mutations of c. 188C>T (p.Arg63Gln) and c. 5374C>T (p.Glu1792Lys) of the DOCK6 gene, which were respectively inherited from his mother and father. Neither mutation was reported previously. Bioinformatic analysis indicated that the two amino acids are highly conserved. According to the ACMG guidelines, the c. 188C>T mutation was predicted as likely pathogenic, while the c. 5374C>T mutation was of uncertain significance. Conclusion The compound heterozygous mutations of c. 188C>T (p.Arg63Gln) and c. 5374C>T (p.Glu1792Lys) of the DOCK6 gene may underlie the disease in this patient.