Biallelic pathogenic variants in POC1A are ultra rare. They have been reported in 13 families as causing either Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis (SOFT) syndrome, or a milder partially overlapping phenotype, variant POC1A-related syndrome. This pleiotropic effect is likely precipitated by the variant's location and respective affected protein domain. Here, we describe seven patients from two consanguineous Omani families with classic SOFT syndrome and a novel homozygous POC1A variant (c.64G>T; p.(Val22Phe)), which is the first one described for the alternative exon 2. This result refines the POC1A mutational spectrum relevant for exertion of the described pleiotropic effect. Furthermore, six of our patients experienced recurrent mild to severe respiratory difficulties that have not been previously reported for SOFT syndrome and may be an underdiagnosed or a genotype-specific complication that warrants attention in future studies. Thus, our study unravels new aspects of the genotype-phenotype correlation suggested by previous reports.

中文翻译：

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选择性剪接外显子中的新型POC1A变异体引起经典的SOFT综合征：7位患者的临床表现。

POC1A中的双等位基因致病变异非常罕见。据报道，在13个家庭中，它们引起身材矮小，甲样发育不全，面部畸形和hypoTrichosis（SOFT）综合征，或出现较轻度的部分重叠表型，与POC1A相关的变异综合征。这种多效性效应可能是由于变体的位置和各自受影响的蛋白质结构域而引起的。在这里，我们描述了来自两个近亲阿曼家族的7名患者，他们患有经典的SOFT综合征和一种新型的纯合POC1A变体（c.64G> T； p。（Val22Phe）），这是第2个外显子的第一个突变体。 POC1A突变谱与发挥所述多效性作用有关。此外，我们的六名患者经历了反复发作的轻度至重度呼吸困难，以前没有关于SOFT综合征的报道，并且可能是诊断不足或基因型特异性并发症，值得在未来的研究中予以关注。因此，我们的研究揭示了以前报道所建议的基因型与表型相关性的新方面。