A case report of a family with Primary familial brain calcification caused by a novel MYORG gene variants
10.3760/cma.j.cn511374-202310-00143
- VernacularTitle:MYORG基因新变异位点致原发性家族性脑钙化一个家系的报道
- Author:
Enkui XIA
1
;
Yixin KANG
;
Xiaosheng ZHENG
;
Wei LUO
Author Information
1. 舟山市第三人民医院（舟山市妇女儿童医院）神经内科，舟山 316000
- Publication Type:Journal Article
- Keywords:
Primary familial brain calcification;
MYORG gene;
Compound heterozygous variants;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(4):474-479
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical characteristics and genetic etiology of a primary familial brain calcification (PFBC) family, and analyze the pathogenic mechanism of MYORG gene variants. Methods:A 17-year-old female who presented to the Second Affiliated Hospital of Zhejiang University School of Medicine on 13 May 2024 with " paroxysmal limb twitching for 1 day" was enrolled. The patient and her parents underwent clinical evaluation and neuroimaging. Peripheral blood was collected for whole exome sequencing (WES). Candidate variants were confirmed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (hereinafter referred to as the ACMG Guidelines). This study was approved by Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (Ethics No. 2020-674). Results:① The patient experienced epileptic seizures. Cranial CT revealed multiple calcifications in the bilateral basal ganglia and cerebellum, with a total calcification score of 23. ② WES identified compound heterozygous variants in MYORG: c. 337_348dup (p.Leu113_Arg116dup), a known pathogenic variant, and c. 1268T>G (p.Val423Gly). Segregation analysis showed that the father carried the c. 337_348dup heterozygous variant, whereas the mother carried the c. 1268T>G heterozygous variant. ③ According to ACMG guidelines, the c. 1268T>G variant was classified as "likely pathogenic" (PM2_Supporting + PM3_Supporting + PP1_Supporting + PP3_Moderate + PP4_Supporting). Conclusion:The novel compound heterozygous MYORG variants c. 337_348dup and c.1268T>G have broadened the mutational spectrum of the MYORG gene and further supported compound heterozygosity as an important genetic mechanism in MYORG-related PFBC.
