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Genes 2016, 7(12), 108; doi:10.3390/genes7120108

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

1
Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, Norway
2
Faculty of Medicine, University of Oslo, 0450 Oslo, Norway
3
Department of Clinical Neurosciences for Children, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0450 Oslo, Norway
4
Center for Hematology and Regenerative Medicine (HERM), Department of Medicine, Karolinska University Hospital Huddinge, 14157 Stockholm, Sweden
Current affiliation: Norwegian National Unit for Newborn Screening, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, 0450 Oslo, Norway.
*
Author to whom correspondence should be addressed.
Academic Editor: Roel Ophoff
Received: 19 September 2016 / Revised: 11 November 2016 / Accepted: 23 November 2016 / Published: 29 November 2016
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

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. View Full-Text
Keywords: cerebellar atrophy; craniofacial dysmorphism; developmental delay; epilepsy; GPI-anchors; MCAHS3; PIGT cerebellar atrophy; craniofacial dysmorphism; developmental delay; epilepsy; GPI-anchors; MCAHS3; PIGT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Skauli, N.; Wallace, S.; Chiang, S.C.C.; Barøy, T.; Holmgren, A.; Stray-Pedersen, A.; Bryceson, Y.T.; Strømme, P.; Frengen, E.; Misceo, D. Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype. Genes 2016, 7, 108.

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