ArticleAmerican journal of human genetics2016
Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review.Frontiers in neurology · 2021Pooled it
- Outcomes of bone marrow mononuclear cell transplantation combined with interventional education for autism spectrum disorder.Stem cells translational medicine · 2021Trial
- Methylome-wide association study of multidimensional resilience.Development and psychopathology · 2025Article
- A Unique Derivative Chromosome 4 with a Predominant 4p16.3 Microduplication Phenotype and a Literature Review.Molecular syndromology · 2025Article
- Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism.Human genomics · 2024Article
- Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.Molecular genetics and metabolism · 2024Article
- The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.Brain : a journal of neurology · 2024Observational
- PIGW-related glycosylphosphatidylinositol deficiency: A case report and literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review.Frontiers in genetics · 2023Article
- Article
- Six years' accomplishment of the Initiative on Rare and Undiagnosed Diseases: nationwide project in Japan to discover causes, mechanisms, and cures.Journal of human genetics · 2022Article
- Ethanolamine-phosphate on the second mannose is a preferential bridge for some GPI-anchored proteins.EMBO reports · 2022Article
- Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy.Nature communications · 2022Article
- Distinct Epileptogenic Mechanisms Associated with Seizures in Wolf-Hirschhorn Syndrome.Molecular neurobiology · 2022Article
- Automatic Detection and Classification of Epileptic Seizures in Patients with Liver Cirrhosis and Overlapping Hev Infection Based on Deep Multimodal Fusion Technology.Contrast media & molecular imaging · 2022Article
- Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants inNeurology. Genetics · 2021Article
- PIGG variant pathogenicity assessment reveals characteristic features within 19 families.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- PIGG defines the Emm blood group system.Scientific reports · 2021Article
- High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.International journal of molecular sciences · 2021Article
- Clinical and genetic characterization of ten Egyptian patients with Wolf-Hirschhorn syndrome and review of literature.Molecular genetics & genomic medicine · 2021Review
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Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits. IGDs mainly manifest as intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms are caused by the decreased surface expression of GPI-APs or by structural abnormalities of GPI. Here, we present five affected individuals (from two consanguineous families from Egypt and Pakistan and one non-consanguineous family from Japan) who show intellectual disability, hypotonia, and early-onset seizures. We identified pathogenic variants in PIGG, a gene in the GPI pathway. In the consanguineous families, homozygous variants c.928C>T (p.Gln310(∗)) and c.2261+1G>C were found, whereas the Japanese individual was compound heterozygous for c.2005C>T (p.Arg669Cys) and a 2.4 Mb deletion involving PIGG. PIGG is the enzyme that modifies the second mannose with ethanolamine phosphate, which is removed soon after GPI is attached to the protein. Physiological significance of this transient modification has been unclear. Using B lymphoblasts from affected individuals of the Egyptian and Japanese families, we revealed that PIGG activity was almost completely abolished; however, the GPI-APs had normal surface levels and normal structure, indicating that the pathogenesis of PIGG deficiency is not yet fully understood. The discovery of pathogenic variants in PIGG expands the spectrum of IGDs and further enhances our understanding of this etiopathogenic class of intellectual disability.
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