Kim So Young, Lee Da-Hye, Han Jin Hee, Choi Byung Yoon
Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam 13496, Korea.
Diagnostics (Basel). 2020 May 12;10(5):296. doi: 10.3390/diagnostics10050296.
Elongation factor Tu guanosine-5'-triphosphate (GTP) binding domain containing 2 () encodes a major component of the spliceosomal GTPase and, if mutated, causes mandibulofacial dysostosis with microcephaly (MFDM; MIM#610536). Despite the increasing number of potentially pathogenic variants reported in the literature, most previous studies have relied solely on in silico prediction of the pathogenic potential of variants, which may result in misclassification of the variant's pathogenicity. Given the importance of the functional verification of variants, we identified a novel splice donor site variant, c.271+1G>A of , whose pathogenicity was clearly verified at the RNA level using a minigene assay. A child with MFDM, mixed hearing loss, microcephaly, and a congenital cardiac defect was identified with this variant, which arose in a de novo fashion. The minigene assay showed erroneous integration of the 118 bp IVS3 of exclusively among the c.271+1G>A variant clone. We first applied the minigene assay to identify the splice function of a splice site variant of , thereby allowing for in vitro functional verification of splice site variants in .
含延伸因子Tu鸟苷-5'-三磷酸（GTP）结合结构域2（ ）编码剪接体GTP酶的主要成分，若发生突变，会导致小头畸形下颌面骨发育不全（MFDM；MIM#610536）。尽管文献中报道的潜在致病变异数量不断增加，但此前大多数研究仅依靠对变异体致病潜力的计算机预测，这可能导致变异体致病性的错误分类。鉴于对 变异体进行功能验证的重要性，我们鉴定出一种新的剪接供体位点变异体，即 的c.271+1G>A，其致病性通过小基因检测在RNA水平得到明确验证。一名患有MFDM、混合性听力损失、小头畸形和先天性心脏缺陷的儿童被鉴定携带此变异体，该变异体为新发。小基因检测显示，仅在c.271+1G>A变异体克隆中出现了 118 bp IVS3的错误整合。我们首次应用小基因检测来鉴定 的一个剪接位点变异体的剪接功能，从而实现对 中剪接位点变异体的体外功能验证。
