Department of Child Health Care, Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.
Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China.
Genes (Basel). 2022 Mar 18;13(3):536. doi: 10.3390/genes13030536.
Variants in NAA15 are closely related to neurodevelopmental disorders (NDDs). In this study, we investigated the spectrum and clinical features of NAA15 variants in a Chinese NDD cohort of 769 children. Four novel NAA15 pathogenic variants were detected by whole-exome sequencing, including three de novo variants and one maternal variant. The in vitro minigene splicing assay confirmed one noncanonical splicing variant (c.1410+5G>C), which resulted in abnormal mRNA splicing. All affected children presented mild developmental delay, and catch-up trajectories were noted in three patients based on their developmental scores at different ages. Meanwhile, the literature review also showed that half of the reported patients with NAA15 variants presented mild/moderate developmental delay or intellectual disability, and possible catch-up sign was indicated for three affected patients. Taken together, our study expanded the spectrum of NAA15 variants in NDD patients. The affected patients presented mild developmental delay, and possible catch-up developmental trajectories were suggested. Studying the natural neurodevelopmental trajectories of NDD patients with pathogenic variants and their benefits from physical rehabilitations are needed in the future for precise genetic counseling and clinical management.
NAA15 变异与神经发育障碍（NDD）密切相关。本研究通过全外显子测序，在 769 名中国 NDD 患儿队列中，调查了 NAA15 变异的谱和临床特征。检测到四种新的 NAA15 致病性变异，包括三种新生变异和一种母源变异。体外 mini 基因剪接试验证实了一种非典型剪接变异（c.1410+5G>C），导致异常 mRNA 剪接。所有受影响的儿童均表现为轻度发育迟缓，根据不同年龄的发育评分，三名患者的发育轨迹有追赶现象。同时，文献复习也表明，有报道的 NAA15 变异患者中，有一半表现为轻度/中度发育迟缓或智力残疾，有三名受影响的患者可能有追赶迹象。总之，本研究扩展了 NAA15 变异在 NDD 患者中的谱。受影响的患者表现为轻度发育迟缓，提示可能有追赶发育轨迹。未来需要研究致病性变异 NDD 患者的自然神经发育轨迹及其从物理康复中获益的情况，以便进行精准的遗传咨询和临床管理。
