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Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype

Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy,...

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Autores principales: Skauli, Nadia, Wallace, Sean, Chiang, Samuel C. C., Barøy, Tuva, Holmgren, Asbjørn, Stray-Pedersen, Asbjørg, Bryceson, Yenan T., Strømme, Petter, Frengen, Eirik, Misceo, Doriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192484/
https://www.ncbi.nlm.nih.gov/pubmed/27916860
http://dx.doi.org/10.3390/genes7120108
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author Skauli, Nadia
Wallace, Sean
Chiang, Samuel C. C.
Barøy, Tuva
Holmgren, Asbjørn
Stray-Pedersen, Asbjørg
Bryceson, Yenan T.
Strømme, Petter
Frengen, Eirik
Misceo, Doriana
author_facet Skauli, Nadia
Wallace, Sean
Chiang, Samuel C. C.
Barøy, Tuva
Holmgren, Asbjørn
Stray-Pedersen, Asbjørg
Bryceson, Yenan T.
Strømme, Petter
Frengen, Eirik
Misceo, Doriana
author_sort Skauli, Nadia
collection PubMed
description Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val) in two brothers with several of the typical features of MCAHS3, but in addition, pyramidal tract neurological signs. Notably, they are the first patients with MCAHS3 without skeletal, cardiac, or genitourinary anomalies. PIGT encodes a crucial subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which catalyzes the attachment of proteins to GPI-anchors, attaching the proteins to the cell membrane. In vitro studies in cells from the two brothers showed reduced levels of GPI-anchors and GPI-anchored proteins on the cell surface, supporting the pathogenicity of the novel PIGT variant.
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spelling pubmed-51924842016-12-30 Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype Skauli, Nadia Wallace, Sean Chiang, Samuel C. C. Barøy, Tuva Holmgren, Asbjørn Stray-Pedersen, Asbjørg Bryceson, Yenan T. Strømme, Petter Frengen, Eirik Misceo, Doriana Genes (Basel) Case Report Biallelic PIGT variants were previously reported in seven patients from three families with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), characterized by epileptic encephalopathy, hypotonia, global developmental delay/intellectual disability, cerebral and cerebellar atrophy, craniofacial dysmorphisms, and skeletal, ophthalmological, cardiac, and genitourinary abnormalities. We report a novel homozygous PIGT missense variant c.1079G>T (p.Gly360Val) in two brothers with several of the typical features of MCAHS3, but in addition, pyramidal tract neurological signs. Notably, they are the first patients with MCAHS3 without skeletal, cardiac, or genitourinary anomalies. PIGT encodes a crucial subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which catalyzes the attachment of proteins to GPI-anchors, attaching the proteins to the cell membrane. In vitro studies in cells from the two brothers showed reduced levels of GPI-anchors and GPI-anchored proteins on the cell surface, supporting the pathogenicity of the novel PIGT variant. MDPI 2016-11-29 /pmc/articles/PMC5192484/ /pubmed/27916860 http://dx.doi.org/10.3390/genes7120108 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Skauli, Nadia
Wallace, Sean
Chiang, Samuel C. C.
Barøy, Tuva
Holmgren, Asbjørn
Stray-Pedersen, Asbjørg
Bryceson, Yenan T.
Strømme, Petter
Frengen, Eirik
Misceo, Doriana
Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title_full Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title_fullStr Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title_full_unstemmed Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title_short Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype
title_sort novel pigt variant in two brothers: expansion of the multiple congenital anomalies-hypotonia seizures syndrome 3 phenotype
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192484/
https://www.ncbi.nlm.nih.gov/pubmed/27916860
http://dx.doi.org/10.3390/genes7120108
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