Abstract：
CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.
摘要：
CAPZA2编码CAPZA的α2亚基，这对人体肌动蛋白聚合和解聚至关重要。然而,对CAPZA2相关疾病的了解仍然有限。迄今为止,只有三例被记录为神经发育异常，如运动发育迟缓，说话延迟,智力残疾,低张力,有癫痫病史.在这项研究中,我们记录了一个癫痫发作的病人，轻度智力残疾,运动发育受损，但未表现出言语延迟或张力减退。病人还反复出现呼吸道感染,胃肠道和过敏性疾病。通过全外显子组测序在CAPZA2基因中检测到一个新的从头剪接变体c.219+1G>A。该变体导致mRNA剪接中的外显子4跳跃，通过RT-PCR和Sanger测序证实。据我们所知,这是人类CAPZA2缺陷的第三项研究，记录第四个明确诊断的病例。此外，这种剪接突变类型是首次报道。我们的研究为CAPZA2相关的非综合征性神经发育障碍的存在提供了额外的支持。我们的发现增加了我们对与CAPZA2缺陷相关的表型范围的理解，并丰富了CAPZA2基因突变谱的知识。
