KDM6B gene variation associated neurological developmental disorder: a case report and literature review
10.3760/cma.j.cn113694-20250828-00514
- VernacularTitle:KDM6B基因变异相关神经系统发育障碍1例并文献复习
- Author:
Liming ZHANG
1
;
Lei LIU
;
Jianwei YANG
;
Hongqi SUN
;
Zhixiao YANG
;
Junmei YANG
Author Information
1. 郑州大学附属儿童医院检验科 郑州市儿童感染与免疫重点实验室，郑州 450018
- Publication Type:Journal Article
- Keywords:
Developmental disabilities;
Mutation;
KDM6B gene;
Whole-exome sequencing
- From:
Chinese Journal of Neurology
2025;58(11):1205-1210
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child. Methods:Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021. His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted. Results:The patient was a one-year-six-month old male, with protruding forehead, joint laxity, distal skeletal abnormalities, and behavioral, cognitive, language, intellectual, and psychomotor development disorder. The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs *9) in exon 11 of the KDM6B gene. This variation was classified as pathogenic (PVS1+PS2+PM2_supporting) according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines, with no prior reports. By literature review, no relevant Chinese literature was retrieved, whereas 4 English literatures were found, reporting 98 patients, totally 99 patients (including this case) with nervous system development disorder due to KDM6B gene variation. The main manifestations were neurodevelopmental disorders such as speech, motor, and behavioral abnormalities, mental retardation, as well as facial deformities, hypotonia, infantile feeding difficulties/gastroesophageal reflux, joint/ligament laxity, and abnormalities of the hands and toes/palms. A total of 83 variation sites were found, including 37 frameshift variations, 18 missense variations, 21 nonsense variations, and 7 splicing variations, all of which were heterozygous variations. Conclusions:The KDM6B gene variation can lead to neurodevelopmental disorder, craniofacial developmental and skeletal abnormalities. The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child. This study extends the spectrum of KDM6B gene variant.
