Lessons learned from 40 novel PIGA patients and a review of the literature
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Lessons learned from 40 novel PIGA patients and a review of the literature. / Bayat, Allan; Knaus, Alexej; Pendziwiat, Manuela; Afenjar, Alexandra; Stefan Barakat, Tahsin; Bosch, Friedrich; Callewaert, Bert; Calvas, Patrick; Ceulemans, Berten; Chassaing, Nicolas; Depienne, Christel; Endziniene, Milda; Ferreira, Carlos R.; Moura de Souza, Carolina Fischinger; Freihuber, Cécile; Ganesan, Shiva; Gataullina, Svetlana; Guerrini, Renzo; Guerrot, Anne Marie; Hansen, Lars; Jezela-Stanek, Aleksandra; Karsenty, Caroline; Kievit, Anneke; Kooy, Frank R.; Korff, Christian M.; Kragh Hansen, Johanne; Larsen, Martin; Layet, Valérie; Lesca, Gaetan; McBride, Kim L.; Meuwissen, Marije; Mignot, Cyril; Montomoli, Martino; Moore, Hannah; Naudion, Sophie; Nava, Caroline; Nougues, Marie Christine; Parrini, Elena; Pastore, Matthew; Schelhaas, Jurgen H.; Skinner, Steven; Szczałuba, Krzysztoł; Thomas, Ashley; Thomassen, Mads; Tranebjærg, Lisbeth; van Slegtenhorst, Marjon; Wolfe, Lynne A.; Lal, Dennis; Gardella, Elena; Bomme Ousager, Lilian; Brünger, Tobias; Helbig, Ingo; Krawitz, Peter; Møller, Rikke S.
I: Epilepsia, Bind 61, Nr. 6, 2020, s. 1142-1155.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Lessons learned from 40 novel PIGA patients and a review of the literature
AU - Bayat, Allan
AU - Knaus, Alexej
AU - Pendziwiat, Manuela
AU - Afenjar, Alexandra
AU - Stefan Barakat, Tahsin
AU - Bosch, Friedrich
AU - Callewaert, Bert
AU - Calvas, Patrick
AU - Ceulemans, Berten
AU - Chassaing, Nicolas
AU - Depienne, Christel
AU - Endziniene, Milda
AU - Ferreira, Carlos R.
AU - Moura de Souza, Carolina Fischinger
AU - Freihuber, Cécile
AU - Ganesan, Shiva
AU - Gataullina, Svetlana
AU - Guerrini, Renzo
AU - Guerrot, Anne Marie
AU - Hansen, Lars
AU - Jezela-Stanek, Aleksandra
AU - Karsenty, Caroline
AU - Kievit, Anneke
AU - Kooy, Frank R.
AU - Korff, Christian M.
AU - Kragh Hansen, Johanne
AU - Larsen, Martin
AU - Layet, Valérie
AU - Lesca, Gaetan
AU - McBride, Kim L.
AU - Meuwissen, Marije
AU - Mignot, Cyril
AU - Montomoli, Martino
AU - Moore, Hannah
AU - Naudion, Sophie
AU - Nava, Caroline
AU - Nougues, Marie Christine
AU - Parrini, Elena
AU - Pastore, Matthew
AU - Schelhaas, Jurgen H.
AU - Skinner, Steven
AU - Szczałuba, Krzysztoł
AU - Thomas, Ashley
AU - Thomassen, Mads
AU - Tranebjærg, Lisbeth
AU - van Slegtenhorst, Marjon
AU - Wolfe, Lynne A.
AU - Lal, Dennis
AU - Gardella, Elena
AU - Bomme Ousager, Lilian
AU - Brünger, Tobias
AU - Helbig, Ingo
AU - Krawitz, Peter
AU - Møller, Rikke S.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - bioinformatical comparison
KW - Fryns syndrome phenotype
KW - genotype-phenotype correlation
KW - mild developmental delay
KW - PIGA
U2 - 10.1111/epi.16545
DO - 10.1111/epi.16545
M3 - Journal article
C2 - 32452540
AN - SCOPUS:85085585320
VL - 61
SP - 1142
EP - 1155
JO - Epilepsia
JF - Epilepsia
SN - 0013-9580
IS - 6
ER -
ID: 243008487