ArticleAmerican journal of human genetics2012
The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Neuropathology of genetically defined malformations of cortical development-A systematic literature review.Neuropathology and applied neurobiology · 2021Pooled it
- A drug repurposing screen reveals dopamine signaling as a candidate therapeutic pathway for PIGA-CDG.PLoS genetics · 2026Article
- Genetic dissection of the role ofiScience · 2026Article
- A drug repurposing screen reveals dopamine signaling as a candidate therapeutic pathway for PIGA-CDG.bioRxiv : the preprint server for biology · 2026Article
- Developmental and epileptic encephalopathies with germlineFrontiers in genetics · 2026Article
- Gene replacement therapy for Piga GPI-anchor deficiency in the developing nervous system.bioRxiv : the preprint server for biology · 2025Article
- Characterizing DNA recognition preferences of transcription factors using global couplings and high-throughput sequencing.Nucleic acids research · 2025Article
- Identification of CNTN2 as a genetic modifier of PIGA-CDG in a family with incomplete penetrance and in Drosophila.American journal of human genetics · 2025Article
- In-Depth Phenotyping ofBiomolecules · 2024Article
- Article
- AAV-based gene therapy ameliorated CNS-specific GPI defect in mouse models.Molecular therapy. Methods & clinical development · 2024Article
- Drosophila models of phosphatidylinositol glycan biosynthesis class A congenital disorder of glycosylation (PIGA-CDG) mirror patient phenotypes.G3 (Bethesda, Md.) · 2024Article
- Neurological Consequences of Congenital Disorders of Glycosylation.Advances in neurobiology · 2023Article
- Article
- The correlation between multiple congenital anomalies hypotonia seizures syndrome 2 and PIGA: a case of novel PIGA germline variant and literature review.Molecular biology reports · 2022Review
- C18orf32 loss-of-function is associated with a neurodevelopmental disorder with hypotonia and contractures.Human genetics · 2022Article
- Ethanolamine-phosphate on the second mannose is a preferential bridge for some GPI-anchored proteins.EMBO reports · 2022Article
- Article
- Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.Nature communications · 2022Article
- Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol glycan class A (PIGA) is involved in the first step of glycosylphosphatidylinositol (GPI) biosynthesis. Many proteins, including CD55 and CD59, are anchored to the cell by GPI. Loss of CD55 and CD59 on erythrocytes causes complement-mediated lysis in paroxysmal nocturnal hemoglobinuria (PNH), a disease that manifests after clonal expansion of hematopoietic cells with somatic PIGA mutations. Although somatic PIGA mutations have been identified in many PNH patients, it has been proposed that germline mutations are lethal. We report a family with an X-linked lethal disorder involving cleft palate, neonatal seizures, contractures, central nervous system (CNS) structural malformations, and other anomalies. An X chromosome exome next-generation sequencing screen identified a single nonsense PIGA mutation, c.1234C>T, which predicts p.Arg412(∗). This variant segregated with disease and carrier status in the family, is similar to mutations known to cause PNH as a result of PIGA dysfunction, and was absent in 409 controls. PIGA-null mutations are thought to be embryonic lethal, suggesting that p.Arg412(∗) PIGA has residual function. Transfection of a mutant p.Arg412(∗) PIGA construct into PIGA-null cells showed partial restoration of GPI-anchored proteins. The genetic data show that the c.1234C>T (p.Arg412(∗)) mutation is present in an affected child, is linked to the affected chromosome in this family, is rare in the population, and results in reduced, but not absent, biosynthesis of GPI anchors. We conclude that c.1234C>T in PIGA results in the lethal X-linked phenotype recognized in the reported family.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.