Clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A
10.3760/cma.j.cn511374-20230116-00028
- VernacularTitle:遗传性痉挛性截瘫5A型一个家系的临床表型及遗传学分析
- Author:
Mengyuan LIU
1
;
Dongxiao LI
;
Yuke LI
;
Daoqi MEI
;
Shijie DONG
;
Yanli WANG
;
Weiyu HU
;
Chao GAO
Author Information
1. 郑州大学附属儿童医院/河南省儿童医院 郑州儿童医院康复医学科，郑州 450018
- Keywords:
Spastic paraplegia 5A;
Trio-Whole genome sequencing;
CYP7B1 gene;
Uniparental disomy
- From:
Chinese Journal of Medical Genetics
2024;41(4):437-442
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A).Methods:A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children′s Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c. 1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously. Conclusion:The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c. 1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.
