Tremblay-Laganière, C;
Kaiyrzhanov, R;
Maroofian, R;
Nguyen, TTM;
Salayev, K;
Chilton, IT;
Chung, WK;
... Campeau, PM; + view all
(2020)
PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations.
Clinical Genetics
10.1111/cge.13877.
(In press).
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Abstract
Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane‐bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi‐allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI‐anchored protein (GPI‐AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant.
| Type: | Article |
|---|---|
| Title: | PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations |
| Location: | Denmark |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/cge.13877 |
| Publisher version: | https://doi.org/10.1111/cge.13877 |
| Language: | English |
| Additional information: | Copyright © 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | GPI, IGD, Iron overload, alkaline phosphatase, delayed myelination, developmental delay, epilepsy, hypotonia, language delay |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10116657 |
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