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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,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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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. |
format | Online Article Text |
id | pubmed-5192484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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