Department of Pediatrics, CHU Sainte-Justine Research Center, University of Montreal, 3175, Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
Pediatric Genetics, Amrita Institute of Medical Sciences and Research Centre (AIMS), Kochi, 682041, India.
Hum Genet. 2021 Jun;140(6):879-884. doi: 10.1007/s00439-020-02251-2. Epub 2021 Jan 2.
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 综合征的特征为耳聋、甲营养不良、骨营养不良、智力障碍和癫痫。本研究中，我们报道了两例不伴耳聋的 DOORS 综合征患者。外显子组测序显示，这两例患者均存在 PIGF（NM_173074.3：c.515C>G，p.Pro172Arg）纯合错义变异。我们通过流式细胞术分析证实了糖基磷脂酰肌醇（GPI）生物合成受损。因此，我们描述了 PIGF 这一新型疾病基因在 DOORS 综合征中的因果作用，并强调了该病与 GPI 缺乏症之间的重叠。每个与 DOORS 综合征和/或遗传性 GPI 缺乏相关的基因都存在相当大的临床变异性，因此即使并非所有特征都被注意到，也应保持高度怀疑。
