Analysis of a three-generation Chinese pedigree affected with Hereditary spastic paraplegia type 3A due to variant of ATL1 gene.
10.3760/cma.j.cn511374-20251021-00619
- Author:
Zhenhua GONG
1
;
Fengjuan HE
;
Changshui CHEN
;
Yu AN
Author Information
1. Department of Clinical Genetics, Huantai Maternal and Child Health Care Hospital, Zibo, Shandong, 256400, China. yu.an@fudan.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Pedigree;
Spastic Paraplegia, Hereditary/genetics*;
Male;
Female;
Asian People/genetics*;
Adult;
Haplotypes;
Membrane Proteins/genetics*;
Exome Sequencing;
GTP-Binding Proteins/genetics*;
Mutation;
Middle Aged;
China;
Genetic Association Studies;
East Asian People
- From:
Chinese Journal of Medical Genetics
2026;43(2):129-135
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a Chinese pedigree affected with Hereditary spastic paraplegia type 3A (SPG3A) and the genotype-phenotype correlation.
METHODS:A three-generation pedigree presented at Huantai Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Whole-exome sequencing (WES) and pedigree analysis was carried out. Candidate variant was validated by Sanger sequencing of the members from the pedigree. Haplotype analysis was used to trace the origin of the variant, and pathogenicity was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-12).
RESULTS:A c.1024C>T (p.Pro342Ser) variant of the ATL1 was identified in the four affected members, including the proband, but none of the three unaffected relatives. Haplotype analysis suggested that the variant was derived from the proband's mother and has co-segregated with the disease phenotype. Based on the guidelines of the ACMG, it was classified as likely pathogenic.
CONCLUSION:The ATL1 c.1024C>T (p.Pro342Ser) variant probably underlay the pathogenesis in this pedigree. Above finding has enriched the mutational spectrum of ATL1 and phenotypic spectrum of SPG3A in the Chinese population, and enabled genetic counseling for this pedigree.
