当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy.

Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy.

Abstract：

:Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs). In this report, we describe 12 individuals from nine unrelated families with 10 different bi-allelic PIGK variants. PIGK encodes a component of the GPI transamidase complex, which attaches the GPI anchor to proteins. Clinical features found in most individuals include global developmental delay and/or intellectual disability, hypotonia, cerebellar ataxia, cerebellar atrophy, and facial dysmorphisms. The majority of the individuals have epilepsy. Two individuals have slightly decreased levels of serum alkaline phosphatase, while eight do not. Flow cytometric analysis of blood and fibroblasts from affected individuals showed decreased cell surface presence of GPI-APs. The overexpression of wild-type (WT) PIGK in fibroblasts rescued the levels of cell surface GPI-APs. In a knockout cell line, transfection with WT PIGK also rescued the GPI-AP levels, but transfection with the two tested mutant variants did not. Our study not only expands the clinical and known genetic spectrum of IGDs, but it also expands the genetic differential diagnosis for cerebellar atrophy. Given the fact that cerebellar atrophy is seen in other IGDs, flow cytometry for GPI-APs should be considered in the work-ups of individuals presenting this feature.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Nguyen TTM,Murakami Y,Mobilio S,Niceta M,Zampino G,Philippe C,Moutton S,Zaki MS,James KN,Musaev D,Mu W,Baranano K,Nance JR,Rosenfeld JA,Braverman N,Ciolfi A,Millan F,Person RE,Bruel AL,Thauvin-Robinet C,Ververi A

doi

10.1016/j.ajhg.2020.03.001

subject

Has Abstract

pub_date

2020-04-02 00:00:00

pages

484-495

issue

4

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(20)30077-X

journal_volume

106

pub_type

杂志文章

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