Genetic Study and Prenatal Diagnosis of Inherited Glycosylphosphatidylinositol Disorders due to Novel Variants in Phosphatidylinositol Glycan Genes.

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
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 He
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引用次数: 0

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.

由磷脂酰肌醇聚糖基因新变异引起的遗传性糖基磷脂酰肌醇疾病的遗传学研究和产前诊断。
遗传性糖基磷脂酰肌醇缺乏症(IGDs)是一组罕见的隐性遗传疾病,其特征是由糖基磷脂酰肌醇锚定生物合成途径中断引起的发育迟缓和早发性癫痫。在这项研究中,我们通过全外显子组测序(WES)从4个IGDs家族中鉴定出8个磷脂酰肌醇聚糖(PIG)基因变异。这些变异包括1个PIGA变异,2个PIGW变异和5个PIGN变异,其中5个是新变异。功能分析证实了PIGN (c.1117-12C>G)和PIGW (c.1112delT和c.659T>G)变异的致病性。根据ACMG/AMP指南,四种新的变异被归类为致病性或可能致病性。家庭1和家庭3在产前诊断后顺利产下健康儿童。本研究确定了4个IGD家系的致病原因,扩大了猪基因的突变谱,为此类家系的生殖干预提供了理论依据。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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