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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MDPI AG
2016-11-01
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| Series: | Genes |
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| Online Access: | http://www.mdpi.com/2073-4425/7/12/108 |
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doaj-4b066bd739d14ac5b7f9a4d779b618c42020-11-24T22:15:57ZengMDPI AGGenes2073-44252016-11-0171210810.3390/genes7120108genes7120108Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 PhenotypeNadia Skauli0Sean Wallace1Samuel C. C. Chiang2Tuva Barøy3Asbjørn Holmgren4Asbjørg Stray-Pedersen5Yenan T. Bryceson6Petter Strømme7Eirik Frengen8Doriana Misceo9Department of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayDepartment of Clinical Neurosciences for Children, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0450 Oslo, NorwayCenter for Hematology and Regenerative Medicine (HERM), Department of Medicine, Karolinska University Hospital Huddinge, 14157 Stockholm, SwedenDepartment of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayCenter for Hematology and Regenerative Medicine (HERM), Department of Medicine, Karolinska University Hospital Huddinge, 14157 Stockholm, SwedenFaculty of Medicine, University of Oslo, 0450 Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayDepartment of Medical Genetics, Oslo University Hospital, 0450 Oslo, NorwayBiallelic 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.http://www.mdpi.com/2073-4425/7/12/108cerebellar atrophycraniofacial dysmorphismdevelopmental delayepilepsyGPI-anchorsMCAHS3PIGT |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Nadia Skauli Sean Wallace Samuel C. C. Chiang Tuva Barøy Asbjørn Holmgren Asbjørg Stray-Pedersen Yenan T. Bryceson Petter Strømme Eirik Frengen Doriana Misceo |
| spellingShingle |
Nadia Skauli Sean Wallace Samuel C. C. Chiang Tuva Barøy Asbjørn Holmgren Asbjørg Stray-Pedersen Yenan T. Bryceson Petter Strømme Eirik Frengen Doriana Misceo Novel PIGT Variant in Two Brothers: Expansion of the Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 Phenotype Genes cerebellar atrophy craniofacial dysmorphism developmental delay epilepsy GPI-anchors MCAHS3 PIGT |
| author_facet |
Nadia Skauli Sean Wallace Samuel C. C. Chiang Tuva Barøy Asbjørn Holmgren Asbjørg Stray-Pedersen Yenan T. Bryceson Petter Strømme Eirik Frengen Doriana Misceo |
| author_sort |
Nadia Skauli |
| title |
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_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_sort |
novel pigt variant in two brothers: expansion of the multiple congenital anomalies-hypotonia seizures syndrome 3 phenotype |
| publisher |
MDPI AG |
| series |
Genes |
| issn |
2073-4425 |
| publishDate |
2016-11-01 |
| 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. |
| topic |
cerebellar atrophy craniofacial dysmorphism developmental delay epilepsy GPI-anchors MCAHS3 PIGT |
| url |
http://www.mdpi.com/2073-4425/7/12/108 |
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