[X-linked Alport syndrome: auditory pathogenic variant features and further genotype-phenotype correlations in female...

Objective:To analyze the audiological characteristics of female patients with X-linked Alport syndrome and to explore the relationship between genotype and phenotype in China. Method:The hearing data of 64 females diagnosed as Alport syndrome was reviewed and analyzed. All coding exons of COL4A5 genes were PCR-amplified and sequenced with genomic DNA, or mRNA of COL4A5 gene was RT-PCR amplified and sequenced with skin fibroblast. Result:The 64 cases who were accompanied by hematuria or proteinuria all received pure tone audiometry and acoustic immitance test. The incidence of hearing loss was 20.31% (13/64). The hearing were bilaterally symmetrical sensorineural deafness, most of which were mild and moderate hearing loss. The hearing curve is the groove curve. Among the 64 patients, 42 kinds of DNA variants were detected in 52 cases. Among the patients with hearing loss, 1 of them was 12 years old and the rest were over 35 years old. Mild mutations in 13 cases (10 cases of normal hearing and 3 cases of mild hearing loss) and severe mutations in in 12 cases ( 6 cases of normal hearing and 6 cases of mild to moderate hearing loss) were found in 25 cases over 35 years old. A total of 26 cases were followed up for 2 years or more, of which 7 cases had a downward trend of hearing loss, decreased about 5 dB each year, and there was no significant change in the hearing of the other patients. Conclusion:Mild and moderate hearing impairment, and groove type of audiometric curve are mainly found in Chinese X-linked Alport syndrome in females. Hearing loss occurs at middle-age. The onset time of hearing loss was later than that of the male, and the severity of hearing loss was lighter than that of the male. In the course of follow-up, some patients had a downward trend in hearing, and there was no significant correlation between the hearing phenotype and the genotype.