Abstract：
Coffin-Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic variants in any of 9 BAF chromatin-remodeling complex encoding genes or the genes SOX11 and PHF6. Herein, we performed whole-exome sequencing (WES) and a series of analyses of growth-related, auditory, and radiological findings in two probands with syndromic sensorineural hearing loss and inner ear malformations who exhibited distinctive facial features, intellectual disability, growth retardation, and fifth finger malformation. Two de novo variants in the SOX11 gene (c.148A>C:p.Lys50Asn; c.811_814del:p.Asn271Serfs*10) were detected in these probands and were identified as pathogenic variants as per ACMG guidelines. These probands were diagnosed as having CSS based upon clinical and genetic findings. This is the first report of CSS caused by variants in SOX11 gene in Chinese individuals. Deleterious SOX11 variants can result in sensorineural hearing loss with inner ear malformation, potentially extending the array of phenotypes associated with these pathogenic variants. We suggest that both genetic and clinical findings be considered when diagnosing syndromic hearing loss.
摘要：
Coffin-Siris综合征（CSS，OMIM＃135900）是一种与神经发育和畸形特征相关的罕见先天性疾病。CSS的主要原因是9个BAF染色质重塑复合物编码基因或SOX11和PHF6基因中的任何一个的致病性变体。在这里，我们进行了全外显子组测序（WES）和一系列与生长相关的分析，听觉,和放射学发现的两个先证者的症状性感觉神经性听力损失和内耳畸形表现出独特的面部特征，智力残疾,生长迟缓,五指畸形.SOX11基因中的两个从头变体（c.148A>C：p。Lys50Asn；c.811_814del：p。在这些先证者中检测到Asn271Serfs*10），并根据ACMG指南将其鉴定为致病性变体。根据临床和遗传发现，这些先证者被诊断为具有CSS。这是中国人SOX11基因变异引起CSS的首次报道。有害的SOX11变体可导致感音神经性听力损失并伴有内耳畸形，可能扩展与这些致病变异相关的一系列表型。我们建议在诊断综合征性听力损失时同时考虑遗传和临床发现。
