Structural eye disorders are increasingly recognised as having a genetic basis, although current genetic testing is limited in its success. De novo missense variants in WDR37 are a recently described cause of a multisystemic syndromic disorder featuring ocular coloboma. This study characterises the phenotypic spectrum of this disorder and reports 2 de novo heterozygous variants (p.Thr115Ile, p.Ser119Tyr) in three unrelated Caucasian individuals. All had a clinical phenotype consisting of bilateral iris and retinal coloboma, developmental delay and additional, variable multisystem features. The variants fall within a highly conserved region upstream of the WD‐repeat domains, within an apparent mutation cluster. Consistent with the literature, intellectual disability, structural eye disorders, epilepsy, congenital heart disease, genitorenal anomalies and dysmorphic facial features were observed. In addition, a broader developmental profile is reported with a more specific musculoskeletal phenotype described in association with the novel variant (p.Thr115Ile). We further expand the phenotypic spectrum of WDR37 ‐related disorders to include those with milder developmental delay and strengthen the association of ocular coloboma and musculoskeletal features. We promote the inclusion of WDR37 on gene panels for intellectual disability, epilepsy and structural eye disorders.

中文翻译：

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扩展了从头WDR37错义变体的表型谱。

尽管目前的基因检测在其成功方面受到限制，但结构性眼疾已被越来越多地认为具有遗传基础。WDR37中的De Novo Missense变体是最近描述的以眼球裂瘤为特征的多系统综合征的病因。这项研究表征了这种疾病的表型谱，并报告了三个不相关的白种人个体中的2个新的杂合变异体（p.Thr115Ile，p.Ser119Tyr）。所有患者的临床表型均由双侧虹膜和视网膜大肠癌，发育延迟和其他可变的多系统特征组成。这些变体属于WD重复域上游的高度保守区域内，位于明显的突变簇内。与文献一致，观察到智力障碍，眼睛结构异常，癫痫，先天性心脏病，生殖器异常和面部畸形。此外，据报道，与新变体（p.Thr115Ile）相关的更具体的肌肉骨骼表型具有更广泛的发展概况。我们进一步扩展了表型与WDR37相关的疾病，包括那些具有较轻的发育延迟的疾病，并加强了眼部大肠癌与肌肉骨骼特征的联系。我们促进将WDR37纳入智障，癫痫和结构性眼部疾病的基因面板中。