EVEN‐PLUS syndrome is a rare condition characterized by its involvement of the Epiphyses, Vertebrae, Ears, and Nose, PLUS other associated findings. We report here the fifth case of EVEN‐PLUS syndrome with novel variants c.818 T > G (p.L273X) and c.955C > T (p.L319F) in the HSPA9 gene identified through whole‐exome sequencing. The patient is the first male known to be affected and presented with additional features not previously described with EVEN‐PLUS syndrome. These features include agenesis of the septum pellucidum, a short chest and sternum, 13 pairs of ribs, a single hemivertebra, laterally displaced nipples, hydronephrosis, unilateral cryptorchidism, unilateral single palmar crease, bilateral clubfoot, and hypotonia. qPCR analysis provides supporting evidence for a nonsense‐mediated decay mechanism for the HSPA9 truncating variant. In silico 3D modeling supports the pathogenicity of the c.955C > T (p.L319F) missense variant. The study presented here further describes the syndrome and broadens its mutational and phenotypic spectrum. Our study also lends support to HSPA9 variants as the underlying etiology of EVEN‐PLUS syndrome and ultimately provides a better understanding of the molecular basis of the condition.

中文翻译：

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EVEN-PLUS综合征：一例HSPA9新变异的病例报告，并有HSPA9基因功能异常的证据。

EVEN-PLUS综合征是一种罕见的疾病，其特征在于由所述的其参与ë piphyses，V ertebrae，ë ARS和Ñ OSE，PLUS其它相关联的调查结果。我们在这里报告EVEN-PLUS新颖综合征的第五变体情况下c.818 T> G（p.L273X）和c.955C> T（p.L319F）在HSPA9通过全外显子组测序鉴定的基因。该患者是已知的第一位受到影响的男性，并表现出以前没有出现过的EVEN-PLUS综合征所描述的其他特征。这些特征包括透明隔的发生，短的胸部和胸骨，13对肋骨，单个半椎骨，侧向移位的乳头，肾积水，单侧隐睾，单侧单掌折痕，双侧马蹄内翻足和肌张力低下。qPCR分析为HSPA9截短变体的无义介导的衰变机制提供了支持证据。在计算机上进行3D建模可支持c.955C> T（p.L319F）错义变体的致病性。本文介绍的研究进一步描述了该综合征，并拓宽了其突变和表型谱。我们的研究也为HSPA9变体是EVEN‐PLUS综合征的潜在病因，最终使人们对病情的分子基础有了更好的了解。