Gu J L, Shangguan S F, Wang J H, Li J Y, Xie H, Qu X, Peng N, Wang X, Xu Q, Zhu Y K, Li X H, Sun X F, Chen X L, Wang L
Department of Child Health Care, Capital Institute of Pediatrics, Beijing 100020, China.
Department of Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2025 May 6;59(5):667-676. doi: 10.3760/cma.j.cn112150-20241204-00975.
To explore the genotype and the clinical phenotype of -related developmental delay in children. A case series study was adopted. Collect clinical data from 10 cases of children with gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children's Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children's neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by . The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant (=-3.101, =0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.
