Bayat, Allan ORCID: 0000-0003-4986-8006, Knaus, Alexej, Pendziwiat, Manuela, Afenjar, Alexandra, Barakat, Tahsin Stefan, Bosch, Friedrich, Callewaert, Bert ORCID: 0000-0002-9743-4205, Calvas, Patrick, Ceulemans, Berten, Chassaing, Nicolas, Depienne, Christel, Endziniene, Milda, Ferreira, Carlos R., Moura de Souza, Carolina Fischinger, Freihuber, Cecile, Ganesan, Shiva, Gataullina, Svetlana, Guerrini, Renzo ORCID: 0000-0002-7272-7079, Guerrot, Anne-Marie, Hansen, Lars, Jezela-Stanek, Aleksandra ORCID: 0000-0001-9814-0324, Karsenty, Caroline, Kievit, Anneke, Kooy, Frank R., Korff, Christian M., Hansen, Johanne Kragh, Larsen, Martin, Layet, Valerie, Lesca, Gaetan, McBride, Kim L., Meuwissen, Marije, Mignot, Cyril, Montomoli, Martino, Moore, Hannah, Naudion, Sophie, Nava, Caroline ORCID: 0000-0003-1272-0518, Nougues, Marie-Christine, Parrini, Elena, Pastore, Matthew, Schelhaas, Jurgen H., Skinner, Steven, Szczaluba, Krzysztol, Thomas, Ashley, Thomassen, Mads, Tranebjaerg, Lisbeth, van Slegtenhorst, Marjon, Wolfe, Lynne A., Lal, Dennis, Gardella, Elena, Ousager, Lilian Bomme, Bruenger, Tobias, Helbig, Ingo, Krawitz, Peter and Moller, Rikke S. (2020). Lessons learned from 40 novel PIGA patients and a review of the literature. Epilepsia, 61 (6). S. 1142 - 1156. HOBOKEN: WILEY. ISSN 1528-1167

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Abstract

Objective To define the phenotypic spectrum of phosphatidylinositol glycan class A protein (PIGA)-related congenital disorder of glycosylation (PIGA-CDG) and evaluate genotype-phenotype correlations. Methods Our cohort encompasses 40 affected males with a pathogenic PIGA variant. We performed a detailed phenotypic assessment, and in addition, we reviewed the available clinical data of 36 previously published cases and assessed the variant pathogenicity using bioinformatical approaches. Results Most individuals had hypotonia, moderate to profound global developmental delay, and intractable seizures. We found that PIGA-CDG spans from a pure neurological phenotype at the mild end to a Fryns syndrome-like phenotype. We found a high frequency of cardiac anomalies including structural anomalies and cardiomyopathy, and a high frequency of spontaneous death, especially in childhood. Comparative bioinformatical analysis of common variants, found in the healthy population, and pathogenic variants, identified in affected individuals, revealed a profound physiochemical dissimilarity of the substituted amino acids in variant constrained regions of the protein. Significance Our comprehensive analysis of the largest cohort of published and novel PIGA patients broadens the spectrum of PIGA-CDG. Our genotype-phenotype correlation facilitates the estimation on pathogenicity of variants with unknown clinical significance and prognosis for individuals with pathogenic variants in PIGA.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bayat, AllanUNSPECIFIEDorcid.org/0000-0003-4986-8006UNSPECIFIED
Knaus, AlexejUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pendziwiat, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Afenjar, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barakat, Tahsin StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosch, FriedrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callewaert, BertUNSPECIFIEDorcid.org/0000-0002-9743-4205UNSPECIFIED
Calvas, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ceulemans, BertenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chassaing, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Depienne, ChristelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endziniene, MildaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferreira, Carlos R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moura de Souza, Carolina FischingerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freihuber, CecileUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganesan, ShivaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gataullina, SvetlanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerrini, RenzoUNSPECIFIEDorcid.org/0000-0002-7272-7079UNSPECIFIED
Guerrot, Anne-MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jezela-Stanek, AleksandraUNSPECIFIEDorcid.org/0000-0001-9814-0324UNSPECIFIED
Karsenty, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kievit, AnnekeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kooy, Frank R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korff, Christian M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Johanne KraghUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Larsen, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Layet, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesca, GaetanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McBride, Kim L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meuwissen, MarijeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mignot, CyrilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montomoli, MartinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naudion, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nava, CarolineUNSPECIFIEDorcid.org/0000-0003-1272-0518UNSPECIFIED
Nougues, Marie-ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parrini, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pastore, MatthewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schelhaas, Jurgen H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skinner, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szczaluba, KrzysztolUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, AshleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tranebjaerg, LisbethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Slegtenhorst, MarjonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfe, Lynne A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gardella, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ousager, Lilian BommeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruenger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helbig, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krawitz, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moller, Rikke S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-332892
DOI: 10.1111/epi.16545
Journal or Publication Title: Epilepsia
Volume: 61
Number: 6
Page Range: S. 1142 - 1156
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1528-1167
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ONSET EPILEPTIC ENCEPHALOPATHIES; GPI-ANCHORED PROTEINS; DEVELOPMENTAL DELAY; GERMLINE MUTATION; BIOSYNTHESIS; VARIANT; FAMILY; PHENOTYPES; SEIZURE; COMPLEXMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33289

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