Clinical and genetic analysis of a child with Spastic paraplegia and psychomotor retardation with or without seizures due to compound heterozygous variants of the HACE1 gene
10.3760/cma.j.cn511374-20240508-00278
- VernacularTitle:HACE1基因复合杂合变异致痉挛性截瘫和精神运动发育迟缓伴或不伴痫性发作1例患儿的临床及遗传学分析
- Author:
Zhengfang CHEN
1
;
Xiaoyan XUAN
1
;
Xiaoke ZHAO
1
Author Information
1. 南京医科大学附属儿童医院/南京儿童医院，南京 210008
- Publication Type:Journal Article
- Keywords:
HACE1 gene;
Psychomotor disorders;
Muscle hypertonia;
Child
- From:
Chinese Journal of Medical Genetics
2025;42(2):156-161
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of a child with Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS).Methods:A child who was admitted to the Children′s Hospital Affiliated to Nanjing Medical University in April 2022 for motor developmental delay, intellectual disability, and hypertonia was selected as the study subject. Relevant clinical data were retrospectively analyzed. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were searched in the Single Nucleotide Polymorphism Database (dbSNP) and Online Mendelian Inheritance in Man (OMIM) database. Pathogenicity of the variants was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using key words such as " HACE1 gene" " Spastic paraplegia and psychomotor retardation with or without seizures" and " SPPRS", previous reports on SPPRS patients due to HACE1 gene variants were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, CQVIP, and PubMed databases, with the time set from January 1, 2000 to April 7, 2024. A mutation map for the HACE1 protein in the patients was created. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Nanjing Medical University (Ethics No. 202404008-1). Results:The clinical manifestations of the child had included motor developmental delay, intellectual disability and hypertonia. Magnetic resonance imaging revealed hypoplasia of posterior corpus callosum and splenium, with slight enlargement of lateral ventricles. WES revealed that the child has harbored compound heterozygous variants of the HACE1 gene, namely c. 535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c. 1678+ 2(IVS15)T>C, which were respectively inherited from his parents. Based on the guidelines from the ACMG, the variants were respectively rated as likely pathogenic (PVS1 + PM2_Supporting) and pathogenic (PVS1 + PM2_Supporting + PM3). Literature search has identified 8 papers, which reported 23 SPPRS cases due to HACE1 gene variants. All patients exhibited psychomotor developmental delay, among whom 18 HACE1 gene variants were identified. Conclusion:The c. 535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c. 1678+ 2(IVS15)T>C compound heterozygous variants of the HACE1 gene probably underlay the pathogenesis of SPPRS in this child. Above discovery has enriched the mutational and phenotypic spectrum of the HACE1 gene and provided a reference for clinical diagnosis and genetic counseling.
