Xu Jinghan, Li Jingjing, Jiao Zhihui, Sun Gege, Chen Duo, Kong Xiangdong, Wang Li
Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Jan 10;40(1):47-52. doi: 10.3760/cma.j.cn511374-20220517-00333.
To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene.
Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.
The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin.
The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
探讨一名因CHAMP1基因变异导致的40型常染色体显性智力障碍（MRD40）患儿的临床及遗传特征。
分析该患儿的临床特征。通过低深度高通量全基因组拷贝数变异测序（CNV-seq）和全外显子测序（WES）进行基因检测。还对因CHAMP1基因变异导致的MRD40患者的临床表型和遗传特征进行了文献综述。
该患儿为11个月大女童，存在智力和运动发育迟缓。CNV-seq未发现明确的致病变异。WES检测到CHAMP1基因存在杂合的c.1908C>G（p.Y636*）变异，其父母均未携带，预测为致病性变异。文献综述从之前的12篇报道中又确定了33名患儿。所有患儿均有发育迟缓及智力障碍，多数有肌张力障碍（94.1%）、语言和/或行走延迟（85.2%，82.4%）以及眼部异常（79.4%）。共检测到CHAMP1基因的26种变异，所有无义变异均为功能丧失型，位于外显子3，且为新发变异。
CHAMP1基因的杂合c.1908C>G（p.Y636*）变异可能是该患儿WRD40的病因。对于有全面发育迟缓、智力障碍、张力亢进及面部畸形的患儿，应考虑进行基因检测。
