Genotype–phenotype correlation of X-linked Alport syndrome observed in both genders: a multicenter study in South Korea

Abstract

Abstract The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype–phenotype correlation not only in male patients but also in female patients with XLAS.