Pathogenic variants in POC1A led to SOFT syndrome and variant POC1A-related (vPOC1A) syndrome. SOFT syndrome is a rare primordial dwarfism condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis.The main clinical differences between SOFT and vPOC1A syndrome include dyslipidemia with insulin resistance and acanthosis nigricans. To our knowledge, this is the first report of a SOFT syndrome patient diagnosed with a homozygous splicing variant, which could help to extend our understanding of the genotypic and phenotypic information of the disease. We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. Laboratory tests displayed mild insulin resistance. Whole-exome sequencing (WES) led to the identification of a homozygous splicing variant (c.981+1G>A) in POC1A gene of the patient, which was inherited from his heterozygous parents confirmed by Sanger sequencing. Further transcriptional experiments of the splicing variant revealed aberrant percentage of exon 9 skipping transcripts. This is the firstly reported case of a SOFT syndrome patient with a novel homozygous splicing variant and detailed delineation of the aberrant transcript in proband and carrier of the variant in Chinese. Our study enriched mutational spectrum of POC1A which could help in further genetic diagnosis and counselling of SOFT syndrome patients.

中文翻译：

---

由 POC1A 致病性纯合剪接变异引起的 SOFT 综合征的鉴定：病例报告


POC1A 的致病变异导致 SOFT 综合征和变异 POC1A 相关 (vPOC1A) 综合征。 SOFT综合征是一种罕见的原始侏儒症，以身材矮小、甲发育不良、面部畸形和少毛症为特征。SOFT与vPOC1A综合征的主要临床差异包括血脂异常伴胰岛素抵抗和黑棘皮症。据我们所知，这是首例被诊断为纯合剪接变异的 SOFT 综合征患者的报告，这可能有助于扩展我们对该疾病的基因型和表型信息的理解。我们报告了一名患有 SOFT 综合征的 7 岁男孩。患者身材矮小，面部特征对称，包括前额突出、倒三角脸、内眦赘皮、牙齿小、耳朵肿大等。实验室测试显示轻度胰岛素抵抗。全外显子组测序（WES）鉴定出患者POC1A基因中存在纯合剪接变异（c.981+1G>A），经桑格测序证实，该变异遗传自其杂合父母。剪接变体的进一步转录实验揭示了外显子 9 跳跃转录本的异常百分比。这是首次报道的具有新型纯合剪接变异的 SOFT 综合征患者病例，并详细描述了先证者和该变异携带者的异常转录本。我们的研究丰富了POC1A的突变谱，有助于SOFT综合征患者的进一步基因诊断和咨询。