PIGF deficiency causes a phenotype overlapping with DOORS syndrome

  • Hum Genet. 2021 Jun;140(6):879-884. doi: 10.1007/s00439-020-02251-2.
Smrithi Salian  1 ,  Hind Benkerroum  1 ,  Thi Tuyet Mai Nguyen  1 ,  Sheela Nampoothiri  2 ,  Taroh Kinoshita  3 ,  Têmis Maria Félix  4 ,  Fiona Stewart  5 ,  Sanjay M Sisodiya  6 ,  Yoshiko Murakami  3 ,  Philippe M Campeau  7
Affiliations
  • 1. Department of Pediatrics, CHU Sainte-Justine Research Center, University of Montreal, 3175, Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
  • 2. Pediatric Genetics, Amrita Institute of Medical Sciences and Research Centre (AIMS), Kochi, 682041, India.
  • 3. Yabumoto Department of Intractable Disease Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
  • 4. Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
  • 5. Northern Ireland Regional Genetics Centre, Belfast, BT97AB, Northern Ireland.
  • 6. NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
  • 7. Department of Pediatrics, CHU Sainte-Justine Research Center, University of Montreal, 3175, Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada. [email protected].
PMID: 33386993 DOI: 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.