EFTUD2基因中的一个新生同义变异破坏正常剪接并导致小头畸形的下颌面部发育不全：病例报告
A de novo synonymous variant in EFTUD2 disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report.
作者信息
Jacob Arthur, Pasquier Jennifer, Carapito Raphael, Auradé Frédéric, Molitor Anne, Froguel Philippe, Fakhro Khalid, Halabi Najeeb, Viot Géraldine, Bahram Seiamak, Rafii Arash
机构信息
Univ. Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199 - EGID, F-59000, Lille, France.
Stem Cell and Microenvironment Laboratory, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.
出版信息
BMC Med Genet. 2020 Sep 17;21(1):182. doi: 10.1186/s12881-020-01121-y.
BACKGROUND
Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene.
CASE PRESENTATION
Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in the EFTUD2 gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon.
CONCLUSIONS
We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.
背景
伴有小头畸形的下颌面骨发育不全（MFDM）是一种罕见的常染色体显性遗传病，其特征为智力和生长发育迟缓以及严重小头畸形，由EFTUD2基因中的错义、剪接位点变异或微缺失引起。
病例报告
在此，我们研究了一名有MFDM症状且核型正常的年轻女孩的病例。对该家族进行全外显子组测序以确定导致此表型的基因改变。我们在EFTUD2基因中鉴定出一个新生同义变异。我们证明该同义变异破坏了内含子9中的供体剪接位点，导致外显子9跳跃以及移码，进而导致提前出现终止密码子。
结论
我们报告了首例由同义变异破坏供体剪接位点导致外显子跳跃而引起的MFDM病例。
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