Department of Nephrology & Rheumatology, Kunming Children's Hospital, Kunming, Yunnan, China.
Dali University, Dali, Yunnan, China.
Medicine (Baltimore). 2021 Nov 24;100(47):e27890. doi: 10.1097/MD.0000000000027890.
Alport syndrome (AS) is an inherited progressive renal failure, characterized by kidney disease, hearing loss, and eye abnormalities.
A 7-year-old male child was admitted for persistent microscopic hematuria and proteinuria.
Combined with clinical manifestations, laboratory testing, pathological changes of kidney and sequencing results, the patient was diagnosed as AS.
The patient was treated with ACEI and tacrolimus drugs for 2 years, but continued to have hematuria and proteinuria. Thus, a genetic analysis was performed using next-generation sequencing in four affected members from the family.
The findings revealed triple compound heterozygous mutation of COL4A4: three novel variations, c.1045C>T (p. R349X), c.3505+1G>A (splicing), and c.2165G>A (p. G722D).
This study was novel in finding that a triple variant of the COL4A4 gene simultaneously in trans and in cis. The effects of multiple mutation sites and the type of gene mutation in AS were also underlined.
Alport 综合征（AS）是一种遗传性进行性肾衰竭，其特征是肾脏疾病、听力损失和眼部异常。
一名 7 岁男性患儿因持续镜下血尿和蛋白尿入院。
结合临床表现、实验室检查、肾脏病理改变和测序结果，该患儿被诊断为 AS。
该患儿接受 ACEI 和他克莫司药物治疗 2 年，但仍有血尿和蛋白尿。因此，对家族中 4 名受影响成员进行了下一代测序的基因分析。
发现 COL4A4 三重复合杂合突变：三个新的变异，c.1045C>T（p.R349X）、c.3505+1G>A（剪接）和 c.2165G>A（p.G722D）。
本研究发现 COL4A4 基因同时存在反式和顺式三重变体，这是新颖的。还强调了 AS 中多个突变位点和基因突变类型的影响。
