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.

DOORS综合征的特征是耳聋，甲状营养不良，骨营养不良，智力障碍和癫痫发作。在这项研究中，我们报告了两个无耳聋的DOORS综合征无关个体。外显子组测序揭示了两者中PIGF的纯合错义变体（NM_173074.3：c.515C> G，p.Pro172Arg）。我们通过流式细胞仪分析证明受损的糖基磷脂酰肌醇（GPI）生物合成。因此，我们描述了一种新的疾病基因PIGF在DOORS综合征中的因果作用，并强调了这种情况与GPI缺乏症之间的重叠。对于每个与DOORS综合征和/或遗传性GPI缺陷有关的基因，其临床变异性都很大，因此即使没有注意到所有特征，也应高度怀疑。