PIGF deficiency causes a phenotype overlapping with DOORS syndrome
- 2 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Human Genetics
- Vol. 140 (6), 879-884
- https://doi.org/10.1007/s00439-020-02251-2
Abstract
DOORS syndrome is characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. In this study, we report two unrelated individuals with DOORS syndrome without deafness. Exome sequencing revealed a homozygous missense variant in PIGF (NM_173074.3:c.515C>G, p.Pro172Arg) in both. We demonstrate impaired glycosylphosphatidylinositol (GPI) biosynthesis through flow cytometry analysis. We thus describe the causal role of a novel disease gene, PIGF, in DOORS syndrome and highlight the overlap between this condition and GPI deficiency disorders. For each gene implicated in DOORS syndrome and/or inherited GPI deficiencies, there is considerable clinical variability so a high index of suspicion is warranted even though not all features are noted.Keywords
Funding Information
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
This publication has 16 references indexed in Scilit:
- TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic featuresNeurology, 2016
- Genotype–phenotype correlation of congenital anomalies in multiple congenital anomalies hypotonia seizures syndrome (MCAHS1)/PIGN‐related epilepsyAmerican Journal of Medical Genetics Part A, 2015
- The TOPCONS web server for consensus prediction of membrane protein topology and signal peptidesNucleic Acids Research, 2015
- New insights into the functions of PIGF, a protein involved in the ethanolamine phosphate transfer steps of glycosylphosphatidylinositol biosynthesisBiochemical Journal, 2014
- The genetic basis of DOORS syndrome: an exome-sequencing studyThe Lancet Neurology, 2013
- Prediction of membrane-protein topology from first principlesProceedings of the National Academy of Sciences, 2008
- The Role of Gas1 in Embryonic Development and its Implications for Human DiseaseCell Cycle, 2007
- GPI7 Is the Second Partner of PIG-F and Involved in Modification of GlycosylphosphatidylinositolJournal of Biological Chemistry, 2005
- Requirement of PIG-F and PIG-O for Transferring Phosphoethanolamine to the Third Mannose in GlycosylphosphatidylinositolJournal of Biological Chemistry, 2000
- The glypican family of heparan sulfate proteoglycans: major cell-surface proteoglycans of the developing nervous system.1996