Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature
(2020) In Journal of Inherited Metabolic Disease 43(6). p.1321-1332- Abstract
We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and... (More)
We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.
(Less)
- author
- organization
- publishing date
- 2020-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- epileptic encephalopathy, exome sequencing, GPI, IGD, PIGQ, rare diseases
- in
- Journal of Inherited Metabolic Disease
- volume
- 43
- issue
- 6
- pages
- 12 pages
- publisher
- Springer
- external identifiers
-
- pmid:32588908
- scopus:85088837199
- ISSN
- 0141-8955
- DOI
- 10.1002/jimd.12278
- language
- English
- LU publication?
- yes
- id
- 6ef070d0-a2d7-4b12-a18c-a9170d2b7094
- date added to LUP
- 2020-08-11 10:12:53
- date last changed
- 2024-05-01 14:45:14
@article{6ef070d0-a2d7-4b12-a18c-a9170d2b7094,
abstract = {{<p>We investigated seven children from six families to expand the phenotypic spectrum associated with an early infantile epileptic encephalopathy caused by biallelic pathogenic variants in the phosphatidylinositol glycan anchor biosynthesis class Q (PIGQ) gene. The affected children were all identified by clinical or research exome sequencing. Clinical data, including EEGs and MRIs, was comprehensively reviewed and flow cytometry and transfection experiments were performed to investigate PIGQ function. Pathogenic biallelic PIGQ variants were associated with increased mortality. Epileptic seizures, axial hypotonia, developmental delay and multiple congenital anomalies were consistently observed. Seizure onset occurred between 2.5 months and 7 months of age and varied from treatable seizures to recurrent episodes of status epilepticus. Gastrointestinal issues were common and severe, two affected individuals had midgut volvulus requiring surgical correction. Cardiac anomalies including arrythmias were observed. Flow cytometry using granulocytes and fibroblasts from affected individuals showed reduced expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Transfection of wildtype PIGQ cDNA into patient fibroblasts rescued this phenotype. We expand the phenotypic spectrum of PIGQ-related disease and provide the first functional evidence in human cells of defective GPI-anchoring due to pathogenic variants in PIGQ.</p>}},
author = {{Johnstone, Devon L. and Nguyen, Thi Tuyet Mai and Zambonin, Jessica and Kernohan, Kristin D. and St-Denis, Anik and Baratang, Nissan V. and Hartley, Taila and Geraghty, Michael T. and Richer, Julie and Majewski, Jacek and Bareke, Eric and Guerin, Andrea and Pendziwiat, Manuela and Pena, Loren D.M. and Braakman, Hilde M.H. and Gripp, Karen W. and Edmondson, Andrew C. and He, Miao and Spillmann, Rebecca C. and Eklund, Erik A. and Bayat, Allan and McMillan, Hugh J. and Boycott, Kym M. and Campeau, Philippe M.}},
issn = {{0141-8955}},
keywords = {{epileptic encephalopathy; exome sequencing; GPI; IGD; PIGQ; rare diseases}},
language = {{eng}},
number = {{6}},
pages = {{1321--1332}},
publisher = {{Springer}},
series = {{Journal of Inherited Metabolic Disease}},
title = {{Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ : Report of seven new subjects and review of the literature}},
url = {{http://dx.doi.org/10.1002/jimd.12278}},
doi = {{10.1002/jimd.12278}},
volume = {{43}},
year = {{2020}},
}