Genetic analysis of a patient with Alport syndrome due to compound heterozygous variants ofCOL4A4 gene
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目的 分析1例Alport综合征患者的临床表型及遗传学特征。 方法 选取2020年11月至郑州大学第一附属医院肾内科就诊的1例Alport综合征患者为研究对象。收集患者的临床资料。应用高通量测序对患者进行COL4A3、COL4A4、COL4A5基因检测，针对候选致病变异进行Sanger测序家系验证。 结果 患者主要临床表现为血尿、蛋白尿、听力下降，听觉相关检查提示双耳对称性耳蜗性感音神经性耳聋，肾穿刺病理活检结果为轻度系膜增生性肾小球肾炎。基因检测发现患者携带COL4A4基因c.940G>A(p.Gly314Ser)和c.3773G>A(p.Gly1258Asp)复合杂合变异，分别为父源性和母源性变异，呈常染色体隐性遗传。该变异既往未见报道，根据美国医学遗传学与基因组学学会相关指南均评估为致病性变异。 结论 COL4A4基因c.940G>A(p.Gly314Ser)和c.3773G>A(p.Gly1258Asp)变异可能为该Alport综合征患者的遗传学病因。上述发现丰富了COL4A4基因的变异谱。 Objective To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome. Methods A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family. Results The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c. 940G>A (p.Gly314Ser) and c. 3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The c. 940G>A (p.Gly314Ser) and c. 3773G>A (p.Gly1258Asp) compound heterozygous variants of theCOL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.
Objective To analyze the clinical phenotype and genetic characteristics of a patient with Alport syndrome. Methods A patient with Alport syndrome who had visited the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the patient were collected. High-throughput sequencing was carried out to detect potential variant of the COL4A3, COL4A4 and COL4A5 genes, and Sanger sequencing was carried out for verification of candidate variants in the family. Results The main clinical manifestations of the patient included hematuria, proteinuria, and impaired hearing. Audiometric testing suggested symmetrical cochlear sensory neural hearing loss on both sides. Renal biopsy revealed mild mesangial proliferative glomerulonephritis. Genetic testing revealed that the patient has harbored compound heterozygous variants of the COL4A4 gene, namely c. 940G>A (p.Gly314Ser) and c. 3773G>A (p.Gly1258Asp), which were respectively inherited from her father and mother. Neither variant has been reported before, and were predicted to be pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The c. 940G>A (p.Gly314Ser) and c. 3773G>A (p.Gly1258Asp) compound heterozygous variants of theCOL4A4 gene probably underlay the Alport syndrome in this patient. Above finding has enriched the mutational spectrum of the COL4A4 gene.
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