OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male

One case of 46, XY partial gonadal dysgenesis due to a congenital defect of DEAH-box RNA helicase 37(DHX37) was reported. The clinical and genetic data of a boy who was admitted to the Department of Endocrinology and Metabolism, the First Affiliated Hospital of Henan University of Science and Technology due to ambiguous external genitalia in September 2020 were collected and analyzed. This 3-month-old male patient showed a micropenis, bilateral cryptorchidism, 46, XY karyotype, a decrease in testosterone, anti-Müllerian hormone, inhibin B, an increase in follicle stimulating hormone. Testis biopsy indicated gonadal dysgenesis. The proband harbored a de novo heterozygous mutation in the DHX37 gene c. 923G>A(p.Arg308Gln). DHX37 variants need to be considered for 46, XY gonadal dysgenesis.