Premium
Genetic Study and Prenatal Diagnosis of Inherited Glycosylphosphatidylinositol Disorders due to Novel Variants in Phosphatidylinositol Glycan Genes
Author(s) -
Zhao ZiXi,
Zhou JingLin,
Wang Qi,
Peng Songmin,
Peng Yao,
Wang YuRong,
Hu Liang,
Aiyitahong Rejima,
Peng Lin,
Gu Feng,
Lu GuangXiu,
Lin Ge,
Chen Song,
Tan YueQiu,
Du Juan,
He WenBin
Publication year - 2025
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.14716
Subject(s) - genetics , biology , gene , pedigree chart , exome sequencing , mutation , exome
ABSTRACT Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare recessive genetic conditions characterised by developmental delays and an early onset epilepsy caused by disruptions in the glycosylphosphatidylinositol‐anchored biosynthetic pathway. In this study, we identified eight variants in phosphatidyl inositol glycan (PIG) genes from four IGDs families through whole‐exome sequencing (WES). The variants included one in PIGA , two in PIGW and five in PIGN , with five being novel variants. Functional analysis confirmed the pathogenicity of the PIGN (c.1117‐12C>G) and PIGW (c.1112delT and c.659T>G) variants. According to ACMG/AMP guidelines, four novel variants were classified as pathogenic or likely pathogenic. Families I and III successfully delivered healthy children after prenatal diagnosis. This study identified the pathogenic causes of four IGD pedigrees, expanded the mutation spectrum of PIG genes and provided a theoretical basis for reproductive interventions in such families.