Clinical characteristics and genetic analysis of CYP7B1 gene mutation-associated complex hereditary spastic paraplegia pedigrees
10.3760/cma.j.cn113694-20231226-00403
- VernacularTitle:CYP7B1基因突变相关的复杂型遗传性痉挛性截瘫家系的临床特征及遗传学分析
- Author:
Yuwei ZHANG
1
;
Jiewen ZHANG
;
Guiyu LOU
;
Bing ZHANG
;
Yusheng CHEN
;
Wenli MEI
;
Na QI
;
Xingxing LEI
;
Ke YANG
Author Information
1. 河南省人民医院医学遗传研究所，郑州 450003
- Keywords:
Spastic paraplegia, hereditary;
CYP7B1 gene;
Mutation
- From:
Chinese Journal of Neurology
2024;57(8):881-889
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical phenotype and genetic characteristics of probands in 3 pedigrees of complex hereditary spastic paraplegia type 5 (HSP5) who developed symptoms during childhood, and the genetic diagnostic methods of HSP5 to improve the diagnosis and differential diagnosis of this disease.Methods:The clinical data of 3 HSP5 families admitted to Henan Provincial People′s Hospital from June 2020 to January 2023 were collected. Whole exome sequencing (WES) was performed on the patients to analyze phenotype-related single nucleotide variation (SNV) and small fragment insertion/deletion (INDEL) variation. At the same time, the sequencing data were used to analyze the dynamic mutation regions of specific genes.Results:The probands in the 3 families had complex HSP: the proband in family 1 showed weakness of both lower limbs, urgency of urination and ataxia; the proband in family 2 showed slightly lower intelligence, weakness of both lower limbs, dysarthria, and brain magnetic resonance imaging showed white matter lesions; the proband in family 3 showed muscle weakness, spasm, frequent urination and ataxia of both lower limbs. The sequencing results showed that the CYP7B1 gene c.1171G>T (paternal) and c.1249C>T (maternal) compound heterozygous mutations were found in proband 1 and his younger brother. The CYP7B1 gene c.334C>T (paternal) and c.259+2T>C (maternal) compound heterozygous mutations were found in proband 2 and her younger sister. The CYP7B1 gene c.334C>T (paternal) and c.1082G>A (maternal) compound heterozygous mutations were found in proband 3. And c.1171G>T was a new variant that had not been reported before. Dynamic mutation analysis showed that the numbers of CAG repeats of ATXN1/2/3/6/7/8/12, DRPLA, TBP genes were within the normal range. According to the clinical manifestations and genetic examination results of the children in the 3 pedigrees, the diagnosis of HSP5 was clear. Conclusions:The 3 families in the study all had complex HSP5 caused by compound heterozygous mutations of the CYP7B1 gene. WES can analyze SNV, INDEL and dynamic mutations simultaneously to make the maximum clear diagnosis and can be used as an effective detection method for HSP5.
