ArticleHuman molecular genetics2015
Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review.Frontiers in neurology · 2021Pooled it
- Reporting a Novel Disease Causing Variant in PGAP3 Associated With Hyperphosphatasia and Intellectual Disability: A Case Report and Comprehensive Literature Review.Molecular genetics & genomic medicine · 2026Review
- Biosynthesis of GPI anchored proteins, its deficiencies and treatment.Journal of human genetics · 2025Review
- Two novel cases with PIGQ-CDG: expansion of the genotype-phenotype spectrum and evaluation of GestaltMatcher as a diagnostic tool.Frontiers in genetics · 2025Article
- The clinical and genetic spectrum of inherited glycosylphosphatidylinositol deficiency disorders.Brain : a journal of neurology · 2024Observational
- Inherited glycosylphosphatidylinositol deficiency: a review from molecular and clinical perspectives.Acta biochimica et biophysica Sinica · 2024Review
- Article
- Genome and RNA sequencing boost neuromuscular diagnoses to 62% from 34% with exome sequencing alone.Annals of clinical and translational neurology · 2024Article
- Functional categorization of gene regulatory variants that cause Mendelian conditions.Human genetics · 2024Review
- Excluding Digenic Inheritance ofGenes · 2023Article
- Hyperphosphatasia with mental retardation syndrome 3: Cerebrospinal fluid abnormalities and correction with pyridoxine and Folinic acid.JIMD reports · 2023Article
- 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
- 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
- Expanding the Phenotypic Spectrum of GPI Anchoring Deficiency Due to Biallelic Variants inNeurology. Genetics · 2021Article
- Article
- The Glycosylphosphatidylinositol biosynthesis pathway in human diseases.Orphanet journal of rare diseases · 2020Review
- Homozygous splice-variants in human ARV1 cause GPI-anchor synthesis deficiency.Molecular genetics and metabolism · 2020Article
- Copy Number Variation of theAnimals : an open access journal from MDPI · 2020Article
Corrections and comments
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Authors and funding
24 authors at 12 institutions in 5 countries.
Funding
Abstract
Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitously expressed in the human body and are important for various functions at the cell surface. Mutations in many GPI biosynthesis genes have been described to date in patients with multi-system disease and together these constitute a subtype of congenital disorders of glycosylation. We used whole exome sequencing in two families to investigate the genetic basis of disease and used RNA and cellular studies to investigate the functional consequences of sequence variants in the PIGY gene. Two families with different phenotypes had homozygous recessive sequence variants in the GPI biosynthesis gene PIGY. Two sisters with c.137T>C (p.Leu46Pro) PIGY variants had multi-system disease including dysmorphism, seizures, severe developmental delay, cataracts and early death. There were significantly reduced levels of GPI-anchored proteins (CD55 and CD59) on the surface of patient-derived skin fibroblasts (∼20-50% compared with controls). In a second, consanguineous family, two siblings had moderate development delay and microcephaly. A homozygous PIGY promoter variant (c.-540G>A) was detected within a 7.7 Mb region of autozygosity. This variant was predicted to disrupt a SP1 consensus binding site and was shown to be associated with reduced gene expression. Mutations in PIGY can occur in coding and non-coding regions of the gene and cause variable phenotypes. This article contributes to understanding of the range of disease phenotypes and disease genes associated with deficiencies of the GPI-anchor biosynthesis pathway and also serves to highlight the potential importance of analysing variants detected in 5'-UTR regions despite their typically low coverage in exome data.
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