Journal of Clinical Pediatrics >
Clinical and genetic analysis of two children with Bain type of X-linked intellectual disability caused by HNRNPH2 gene variations based on XCI analysis
Received date: 2025-05-16
Accepted date: 2025-09-25
Online published: 2026-03-06
Objective To investigate the clinical manifestations and genetic characteristics of 2 patients with intellectual disability, X-linked, syndromic, Bain type (MRXSB). Methods Two female children who visited the hospital due to "global growth and development delay and intellectual disability" in January 2023 and November 2023 were taken as the research subjects, and the clinical data of the probands were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing verification were performed on the proband and his family. The methylation-sensitive sites were analyzed by using the XCI detection kit (XCI Filer), and the degree of X chromosome bias inactivation was quantitatively analyzed in combination with capillary electrophoresis. Bioinformatics tools were used to predict the pathogenicity of variations. Results The two children were girls aged 11 and 10 months respectively, both presenting with global growth and development delay, intellectual disability, hypotonia and absence of motor milestones. Among them, proband 1 was accompanied by feeding difficulties, dysphagia and shortness of breath symptoms. The results of trio-WES indicated that both of the two children had heterozygous variations of c.616C>T(p.Arg206Trp) in the HNRNPH2 gene (NM_019597), and Sanger sequencing verification suggested that the variations were all spontaneous variations. XCI analysis indicated that both of the two children had X chromosome bias inactivation, with bias rates of 17.3% and 14.0% respectively. Conclusions This study diagnosed for the first time two girls with MRXSB whose age of onset was<1 year old. Through XCI analysis, it was found that the X chromosomes of all the children were inactivated due to bias. Combined with the earlier and more typical clinical phenotypes of the patients, it was speculated that the degree of XCI bias in all the children might be correlated with the severity of the phenotype. XCI is the core regulatory mechanism of clinical heterogeneity in female XLID. The combination of XCI and trio-WES is of great value for the early diagnosis and prognosis evaluation of female XLID.
SHEN Zihan , ZHANG Chuan , ZHENG Lei , ZHOU Bingbo , TIAN Xinyuan , WANG Yupei , HUI Ling . Clinical and genetic analysis of two children with Bain type of X-linked intellectual disability caused by HNRNPH2 gene variations based on XCI analysis[J]. Journal of Clinical Pediatrics, 2026 , 44(3) : 192 -201 . DOI: 10.12372/jcp.2026.25e0552
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