PIGG variant pathogenicity assessment reveals characteristic features within 19 families.

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Camille Tremblay-LaganièreYoshiko Murakami

Abstract

Phosphatidylinositol Glycan Anchor Biosynthesis, class G (PIGG) is an ethanolamine phosphate transferase catalyzing the modification of glycosylphosphatidylinositol (GPI). GPI serves as an anchor on the cell membrane for surface proteins called GPI-anchored proteins (GPI-APs). Pathogenic variants in genes involved in the biosynthesis of GPI cause inherited GPI deficiency (IGD), which still needs to be further characterized. We describe 22 individuals from 19 unrelated families with biallelic variants in PIGG. We analyzed GPI-AP surface levels on granulocytes and fibroblasts for three and two individuals, respectively. We demonstrated enzymatic activity defects for PIGG variants in vitro in a PIGG/PIGO double knockout system. Phenotypic analysis of reported individuals reveals shared PIGG deficiency-associated features. All tested GPI-APs were unchanged on granulocytes whereas CD73 level in fibroblasts was decreased. In addition to classic IGD symptoms such as hypotonia, intellectual disability/developmental delay (ID/DD), and seizures, individuals with PIGG variants of null or severely decreased activity showed cerebellar atrophy, various neurological manifestations, and mitochondrial dysfunction, a feature increasingly recogni...Continue Reading

References

Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Apr 28, 2006·Pediatric Neurology·Miles D ThompsonPaul A Hwang
May 5, 2010·Journal of Inherited Metabolic Disease·Richard J T Rodenburg
Sep 21, 2013·Neurology·Ichiro KukiYoshiko Murakami
Apr 18, 2015·Orphanet Journal of Rare Diseases·Maja Tarailo-GraovacClara D M van Karnebeek
Nov 19, 2015·Nucleic Acids Research·Chunlei WuAndrew I Su
Dec 30, 2015·Nature Genetics·Xin ZhouJinghui Zhang
Mar 22, 2016·American Journal of Human Genetics·Periklis MakrythanasisYoshiko Murakami
Aug 5, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Anath C LionelChristian R Marshall
Jul 29, 2018·Clinical Genetics·Kara Bellai-DussaultPhilippe M Campeau
Oct 31, 2018·Bioinformatics·Christos KopanosAndreas Massouras
Nov 6, 2018·Nucleic Acids Research·UNKNOWN UniProt Consortium
Mar 12, 2020·Open Biology·Taroh Kinoshita
May 27, 2020·Epilepsia·Allan BayatRikke S Møller

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