Song Chuanlu, Su Jingyu
Genetic Science and Medical Genetics Laboratory, Qinzhou Maternal and Child Health Care Hospital, Qinzhou, Guangxi 535099, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Sep 10;41(9):1105-1109. doi: 10.3760/cma.j.cn511374-20230829-00096.
To explore the genetic basis for a child with pachygyria.
A proband who had visited Qinzhou Maternal and Child Health Care Hospital for pachygyria and mental retardation in June 2020 was selected as the study subject. Clinical data was collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing.
The proband, a 4-year-and-6-month-old female, was clinically diagnosed with megagyrus deformity. WES revealed that she has harbored compound heterozygous variants of the ADGRG1 gene, namely c.781G>T (p.E261*) in exon 6 and c.1369A>C (p.S457R) in exon 11, which were verified by Sanger sequencing to be derived from her mother and father, respectively. Her younger sister was also heterozygous for the c.1369A>C (p.S457R) variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PVS1+PM2_ Supporting; PM1+PM2_Supporting+PM3+PP3).
The c.781G>T (p.E261*) and c.1369A>C (p.S457R) compound heterozygous variants of the ADGRG1 gene probably underlay the pachygyria malformation in this child.
探究一名巨脑回患儿的遗传基础。
选取一名于2020年6月因巨脑回和智力发育迟缓就诊于钦州市妇幼保健院的先证者作为研究对象。收集临床资料。对该患儿进行全外显子组测序（WES），并通过桑格测序验证候选变异。
该先证者为一名4岁6个月大的女性，临床诊断为巨脑回畸形。WES显示她携带ADGRG1基因的复合杂合变异，即外显子6中的c.781G>T（p.E261*）和外显子11中的c.1369A>C（p.S457R），桑格测序验证分别来自其母亲和父亲。她的妹妹也为c.1369A>C（p.S457R）变异的杂合子。根据美国医学遗传学与基因组学学会（ACMG）的指南，这两个变异均被评为可能致病（PVS1+PM2_支持；PM1+PM2_支持+PM3+PP3）。
ADGRG1基因的c.781G>T（p.E261*）和c.1369A>C（p.S457R）复合杂合变异可能是该患儿巨脑回畸形的病因。
