16个中国家庭的Alport综合征基因诊断
Genetic diagnosis of Alport syndrome in 16 Chinese families.
作者信息
Xiao Tangli, Zhang Jun, Liu Li, Zhang Bo
机构信息
Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, P.R. China.
出版信息
Mol Genet Genomic Med. 2024 Mar;12(3):e2406. doi: 10.1002/mgg3.2406.
BACKGROUND
Alport syndrome (AS) is a genetically heterogeneous disorder resulting from mutations in the collagen IV genes COL4A3, COL4A4, and COL4A5. The genetic diagnosis of AS is very important to make precise diagnosis and achieve optimal outcomes.
METHODS
In this study, 16 Chinese families with suspected AS were recruited after pedigree analysis, and the clinical presentations were analyzed by a nephrologist. The genetic diagnosis was performed by whole-exome sequencing (WES) and the disease-causing variants were confirmed by Sanger sequencing.
RESULTS
The cohort of probands included seven men and nine women, with a mean age of 19.9 years. Pathological analysis showed slight-to-moderate mesangial proliferation, and thin basement membrane was the main findings. Pathogenic variants were revealed by WES in each family, and the co-segregation with renal presentation was confirmed by PCR. In addition, RT-PCR analysis showed that the intronic variant led to aberrant splicing.
CONCLUSION
Our findings expand the spectrum of AS gene variation, which will inform genetic diagnosis and add to the theoretical basis for the prevention of AS.
背景
Alport综合征（AS）是一种由IV型胶原基因COL4A3、COL4A4和COL4A5突变引起的遗传异质性疾病。AS的基因诊断对于做出准确诊断和取得最佳治疗效果非常重要。
方法
在本研究中，经系谱分析招募了16个疑似AS的中国家庭，由肾病学家分析其临床表现。通过全外显子组测序（WES）进行基因诊断，并通过桑格测序确认致病变异。
结果
先证者队列包括7名男性和9名女性，平均年龄为19.9岁。病理分析显示轻度至中度系膜增生，主要表现为基底膜变薄。WES在每个家庭中均发现了致病变异，并通过PCR证实其与肾脏表现的共分离。此外，逆转录聚合酶链反应（RT-PCR）分析表明内含子变异导致异常剪接。
结论
我们的研究结果扩展了AS基因变异谱，这将为基因诊断提供信息，并为AS的预防增添理论依据。
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