Zhang Xinli, Shen Xueping, Fan Lihong, Zhang Jinghui
Medical Laboratory Center, Huzhou Maternity and Child Health Care Hospital, Huzhou, Zhejiang 313000, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 May 10;42(5):613-620. doi: 10.3760/cma.j.cn511374-20241231-00697.
To explore the clinical characteristics and genetic etiology of a patient with Weiss-Kruszka syndrome (WSKA).
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).
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).
The ZNF462 c.945_946del variant probably underlay the WSKA in this patient. Above finding has enriched the mutational spectrum of the ZNF462 gene.
探讨一名患有魏斯-克鲁什卡综合征（WSKA）患者的临床特征及遗传病因。
选取2024年10月至12月在湖州市妇幼保健院就诊的一名婚后原发性不孕1年、智力障碍且伴有上睑下垂的男性患者作为研究对象。采集患者及其家庭成员的外周血样本。提取基因组DNA后，进行全外显子测序（WES）。通过桑格测序和生物信息学分析对候选变异进行验证。本研究经医院伦理委员会批准（伦理编号：2023-R-010）。
该患者为29岁男性，表现为身材矮小、三角头畸形、双侧上睑下垂、眉弓高耸、短指畸形、皮肤褶皱过多、蹼颈、多毛症、轻度智力障碍和言语障碍。WES显示他携带ZNF462基因的一个新生杂合移码变异，即c.945_946del（p.T316Rfs*42）。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被分类为致病（PM2_Supporting+PVS1+PM6_Supporting）。
ZNF462基因的c.945_946del变异可能是该患者WSKA的病因。上述发现丰富了ZNF462基因的突变谱。
