Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Beijing Chigene Translational Medical Research Center Co, Beijing, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2309. doi: 10.1002/mgg3.2309. Epub 2023 Oct 25.
COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway. To date, 59 cases of COPA have been reported worldwide.
In this case, Trio-whole exome sequencing was employed in the proband and her parents to identify the underlying genetic cause. COPA variant were detected and the clinical presentation of the patient was described.
Herein, we report a case of a 5-year-old girl with COPA syndrome who presented with symptoms of arthritis combined with Anti-neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV), and progressive renal decline with minimal pulmonary involvement. Trio-whole exome sequencing was performed which revealed a novel heterozygous likely pathogenic variation in the COPA gene (c.679C>T,p.Arg227Cys), which was maternally inherited. Her mother was a heterozygote, but she had no phenotypic manifestations. No other mutations associated with the clinical phenotype were identified.
The present identification and characterization of a novel mutation expands the genotypic spectra of the COPA syndrome and provide reference data to guide future clinical diagnosis and treatment of COPA syndrome.
COPA 综合征是一种新近描述的罕见单基因常染色体显性遗传病，由衣壳蛋白复合物 I（COPI）α亚基的 Coatomer Protein Subunit alpha（COPA）基因突变引起，该基因突变通常为杂合错义突变。其主要临床表现为肺部炎症、关节炎和肾脏疾病。COPA 综合征中的炎症发生可能与异常自噬反应和 I 型干扰素通路异常激活有关。截至目前，全球已报道 59 例 COPA 综合征病例。
本研究对先证者及其父母进行了 Trio-全外显子组测序，以确定潜在的遗传病因。检测 COPA 变异，并描述患者的临床表现。
本文报道了一例 5 岁女孩 COPA 综合征病例，其表现为关节炎合并抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV），且伴有进行性肾功能下降但肺部受累轻微。对 Trio-全外显子组测序显示，该患者 COPA 基因存在一个新的杂合可能致病性变异（c.679C>T，p.Arg227Cys），该变异为母系遗传。其母亲为杂合子，但无表型表现。未发现与该临床表型相关的其他突变。
本研究中鉴定和表征的新型突变扩展了 COPA 综合征的基因型谱，并为指导未来 COPA 综合征的临床诊断和治疗提供了参考数据。
