Zhou Cong, Xiao Yuanyuan, Wei Xing, Wang Jing, Liu Shanling
Department of Medical Genetics / Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Front Genet. 2025 Aug 29;16:1580864. doi: 10.3389/fgene.2025.1580864. eCollection 2025.
Alport syndrome (AS) is an inherited disorder affecting basement membrane collagen IV. AS is characterized by hematuria and progressive renal failure, accompanied by high-frequency sensorineural deafness and ocular changes. AS is caused by collagen type IV α3 chain (), α4 chain (), and α5 chain () variants. We aimed to identify the genetic variants in a cohort of 20 children with clinically suspected AS in Southwest China.
We detected 21 , , and variants in 20 probands. Of these variants, 16 (16/21, 76.2%) were classified as pathogenic/likely pathogenic and 5 (5/21, 23.8%) of uncertain significance according to the American College of Medical Genetics and Genomics criteria. A total of 11 (11/21, 52.4%) and 10 (10/21, 47.6%) variants were known and novel, respectively.
We performed molecular diagnosis on 15 patients using targeted exome sequencing. Our findings indicate additional , , and variants as involved in AS, having implications for genetic diagnosis, therapy, and counseling of affected families.
Alport综合征（AS）是一种影响基底膜胶原蛋白IV的遗传性疾病。AS的特征为血尿和进行性肾衰竭，伴有高频感音神经性耳聋和眼部改变。AS由IV型胶原蛋白α3链（）、α4链（）和α5链（）变异引起。我们旨在确定中国西南部20名临床疑似AS儿童队列中的基因变异。
我们在20名先证者中检测到21种、和变异。根据美国医学遗传学与基因组学学会标准，这些变异中，16种（16/21，76.2%）被分类为致病性/可能致病性，5种（5/21，23.8%）意义不明确。分别共有11种（11/21，52.4%）和10种（10/21，47.6%）变异是已知的和新发现的。
我们使用靶向外显子组测序对15名患者进行了分子诊断。我们的研究结果表明，还有其他、和变异与AS有关，这对受影响家庭的基因诊断、治疗和咨询具有重要意义。
