Genetic analysis of a patient with Weiss-Kruszka syndrome due to variant of ZNF462 gene.
10.3760/cma.j.cn511374-20241231-00697
- Author:
Xinli ZHANG
1
,
2
;
Xueping SHEN
;
Lihong FAN
;
Jinghui ZHANG
Author Information
1. Medical Laboratory Center, Huzhou Maternity and Child Health Care Hospital, Huzhou, Zhejiang 313000, China. xinli.66@
2. com.
- Publication Type:English Abstract
- MeSH:
Humans;
Male;
Adult;
Intellectual Disability/genetics*;
Transcription Factors/genetics*;
Exome Sequencing;
Mutation;
Abnormalities, Multiple/genetics*;
Blepharoptosis/genetics*
- From:
Chinese Journal of Medical Genetics
2025;42(5):613-620
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA).
METHODS:A male patient presented with primary infertility for 1 year post-marriage, intellectual disability, and blepharoptosis at Huzhou Maternity and Child Health Care Hospital from October to December 2024 was selected as the study subject. Peripheral blood samples were collected from the patient and his family members. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Ethics Committee of the Hospital (Ethics No. 2023-R-010).
RESULTS:The patient, a 29-year-old male, had exhibited short stature, trigonocephaly, bilateral blepharoptosis, arched eyebrows, brachydactyly, redundant skin folds, webbed neck, hypertrichosis, mild intellectual disability, and speech impairment. WES revealed that he has harbored a de novo heterozygous frameshifting variant of the ZNF462 gene, namely c.945_946del (p.T316Rfs*42). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM2_Supporting+PVS1+PM6_Supporting).
CONCLUSION:The ZNF462 c.945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.
