Genetic Study and Prenatal Diagnosis of Inherited Glycosylphosphatidylinositol Disorders due to Novel Variants in Phosphatidylinositol Glycan Genes
Zi‐Xi Zhao, Jing‐Lin Zhou, Qi Wang, Songmin Peng, Yao Peng, Yu‐Rong Wang, Liang Hu, Rejima Aiyitahong, Lin Peng, Feng Gu, Guang‐Xiu Lu, Ge Lin, Song Chen, Yue‐Qiu Tan, Juan Du, Wen‐Bin HeABSTRACT
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.