PIGF deficiency causes a phenotype overlapping with DOORS syndrome

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.

Automated summary

DOORS syndrome is a rare disorder characterized by a range of symptoms, including deafness, intellectual disability, and others. This study identified two individuals with DOORS syndrome but without deafness, both carrying a homozygous missense variant in the PIGF gene. The study highlights the variability of clinical features in DOORS syndrome and the importance of considering inherited GPI deficiencies in diagnosis.