Clinical features and genetic analysis of 17 Chinese pedigrees affected with X-linked intellectual disability
10.3760/cma.j.cn511374-20230808-00048
- VernacularTitle:X连锁智力障碍17个家系的临床特征及遗传学分析
- Author:
Yan LI
1
;
Litao QIN
;
Ke YANG
;
Xin CHEN
;
Hongjie ZHU
;
Luya MI
;
Yaoping WANG
;
Xinrui MA
;
Shixiu LIAO
Author Information
1. 郑州大学人民医院 河南省人民医院 河南省人民医院医学遗传研究所 河南省遗传性疾病功能基因组重点实验室，郑州 450003
- Keywords:
Genes, X-Linked;
Intellectual disability;
Trio-Whole exome sequencing;
X chromosome inactivation
- From:
Chinese Journal of Medical Genetics
2024;41(5):533-539
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.
