Clinical, histological and molecular characteristics of Alport syndrome in Chinese children

BACKGROUND: Alport syndrome is caused by COL4A3, COL4A4, or COL4A5 gene mutations. The present study aims to compare the clinicopathological features, gene mutations, and outcome of Chinese children with different forms of Alport syndrome. METHODS: One hundred twenty-eight children from 126 families diagnosed with Alport syndrome through pathological and genetic examination between 2003 and 2021 were included in this single-center retrospective study. The laboratory and clinicopathological features of the patients with different inheritance patterns were analyzed. The patients were followed-up for disease progression and phenotype-genotype correlation. RESULTS: Of the 126 Alport syndrome families, X-linked forms accounted for 77.0%, autosomal recessive for 11.9%, autosomal dominant for 7.1%, and digenic for 4.0%. Among the patients, 59.4% were males and 40.6% were females. Altogether, 114 different mutations were identified in 101 patients from 99 families by whole-exome sequencing, of which 68 have not been previously reported. The most prevalent type of mutation was glycine substitution, which was identified in 52.1%, 36.7%, and 60% of the patients with X-linked Alport syndrome, autosomal recessive and autosomal dominant Alport syndrome, respectively. At the end of a median follow up of 3.3 (1.8-6.3) years, Kaplan-Meier curves showed kidney survival was significantly lower in autosomal recessive compared to X-linked Alport syndrome (P = 0.004). Pediatric patients with Alport syndrome seldom presented extrarenal involvement. CONCLUSIONS: X-linked Alport syndrome is the most frequent form found in this cohort. Progression was more rapid in autosmal recessive than in X-linked Alport syndrome.