EVEN-PLUS综合征是一种罕见的疾病,其特征在于它涉及的骨生病,椎骨,耳朵,还有鼻子,加上其他相关发现。我们在此报告第五例EVEN-PLUS综合征,具有新的变异c.818T>G(p。L273X)和c.955C>T(p。L319F)在通过全外显子组测序鉴定的HSPA9基因中。该患者是已知受影响的第一位男性,并具有之前未描述的EVEN-PLUS综合征的其他特征。这些特征包括透明隔的发育不全,胸部和胸骨短,13对肋骨,一个半椎骨,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,和低张力。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。计算机3D建模支持c.955C>T的致病性(p。L319F)错义变体。本文提出的研究进一步描述了该综合征并扩大了其突变和表型谱。我们的研究还支持HSPA9变体作为EVEN-PLUS综合征的潜在病因,并最终提供了对该病症的分子基础的更好理解。
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.