Analysis of a Chinese pedigree affected with X-linked cardiac valve dysplasia and chronic idiopathic intestinal pseudo obstruction due to a c. 443A>G variant of FLNA gene
10.3760/cma.j.cn511374-20250210-00064
- VernacularTitle:FLNA基因c.443A>G变异所致X连锁心脏瓣膜发育不良伴先天性慢性假性肠梗阻一个家系的研究
- Author:
Tingting JI
1
;
Jiao LIU
;
Yabing ZHANG
;
Qimin TIAN
;
Bin MAO
;
Xiaoling MA
Author Information
1. 兰州大学第一临床医学院，兰州 730013
- Publication Type:Journal Article
- Keywords:
X-linked cardiac valvular dysplasia;
X-linked chronic idiopathic intestinal pseudo-obstruction;
FLNA gene;
Whole-exome sequencing
- From:
Chinese Journal of Medical Genetics
2025;42(5):603-607
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and chronic idiopathic intestinal pseudo-obstruction (CIIPX).Methods:A pedigree presented at the First Hospital of Lanzhou University in June 2024 for CVDPX combined with CIIPX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15).Results:Both the proband and his affected younger brother were found to harbor a hemizygous c. 443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded by the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+ PS4+ PP2+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. Conclusion:This study confirmed the diagnosis of CVDPX/CIIPX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
