Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Mol Genet Genomic Med. 2020 Sep;8(9):e1377. doi: 10.1002/mgg3.1377. Epub 2020 Jun 29.
Syndromic microphthalmia-9 (MCOPS9) is a rare autosomal recessive disorder caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. This disorder is characterized by bilateral clinical anophthalmia, pulmonary hypoplasia/aplasia, cardiac malformations, and diaphragmatic defects. The clinical characteristics of this disorder have not been fully determined because of the rarity of clinical reports.
A comprehensive genotyping examination including copy number variation sequencing (CNV-Seq) and whole-exome sequencing (WES) was applied to a fetus of Han Chinese with bilateral anophthalmia, bilateral pulmonary agenesis, interrupted aortic arch type A, and left ventricular non-compaction (LVNC).
No aneuploidy or pathogenic CNV were identified by CNV-seq. WES analysis revealed a previously reported homozygous splice site (NM_022369.4:c.113+3_113+4del) in the STRA6 gene. This variant was confirmed by Sanger sequencing. The diagnosis of MCOPS9 was confirmed given the identification of the STRA6 mutation and the association of bilateral anophthalmia, pulmonary agenesis, and cardiac malformations.
This case adds to the phenotypic spectrum of MCOPS9, supporting the association with LVNC, and the presence of interruption of aortic arch further demonstrates the variability of the cardiac malformations.
综合征性小眼球-9（MCOPS9）是一种罕见的常染色体隐性遗传病，由 STRA6 基因突变引起，该基因是维生素 A 和视黄酸代谢的重要调节因子。该疾病的特征为双侧临床无眼症、肺发育不全/发育不良、心脏畸形和膈肌缺陷。由于临床报告罕见，该疾病的临床特征尚未完全确定。
对一名双侧无眼症、双侧肺不发育、A型主动脉中断和左心室心肌致密化不全（LVNC）的汉族胎儿进行了全面的基因分型检查，包括拷贝数变异测序（CNV-Seq）和全外显子组测序（WES）。
CNV-seq 未发现非整倍体或致病性 CNV。WES 分析显示 STRA6 基因中存在一个先前报道的纯合剪接位点（NM_022369.4：c.113+3_113+4del）。该变体通过 Sanger 测序得到确认。鉴于 STRA6 基因突变的鉴定以及双侧无眼症、肺不发育和心脏畸形的关联，诊断为 MCOPS9。
该病例增加了 MCOPS9 的表型谱，支持与 LVNC 的关联，且主动脉弓中断的存在进一步证明了心脏畸形的多样性。
