Identification of SPAST gene variant in a pedigree affected with hereditary spastic paraplegia type 4.
10.3760/cma.j.cn511374-20191120-00592
- Author:
Na QI
1
;
Mingming MA
;
Ke YANG
;
Guiyu LOU
;
Litao QIN
;
Qiaofang HOU
;
Yuwei ZHANG
;
Shixiu LIAO
Author Information
1. Institute of Medical Genetics, Henan Provincial People's Hospital, Department of Neurology, Henan Provincial People's Hospital, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory for Birth Defect Prevention, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.1004946490@ qq.com.
- Publication Type:Journal Article
- MeSH:
Base Sequence;
Humans;
Mutation;
Paraplegia/genetics*;
Pedigree;
Sequence Analysis, DNA;
Spastic Paraplegia, Hereditary/genetics*;
Spastin/genetics*
- From:
Chinese Journal of Medical Genetics
2020;37(11):1261-1264
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4).
METHODS:Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing.
RESULTS:DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic.
CONCLUSION:The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.
