Abstract:

Objective To explore the clinical characteristics and genotype of children with Alport syndrome (AS) combined with gap junction protein beta 2 (GJB2) gene mutation induced-deafness. Methods A retrospective analysis of the clinical data and genetic testing results of one child with AS, who admitted to the Department of Nephrology, Xi'an Children's Hospital was performed. Results The children (female) was 3 years old and 8 months old, and the disease started with hematuria and proteinuria. Renal pathology revealed mild mesangial proliferative glomerulonephritis by light microscopy (LM), thin basement membrane nephropathy (TBMN) by electron microscopy (EM), and mild sensorineural deafness in the left ear by hearing test. Genetic testing indicated the presence of C.555 (exon10) -C.568 (exon10) delTGGTCCCACTGGTA (framesshift mutation) in collagen type Ⅳ alpha 5 chain (COL4A5) gene, leading to amino acid change p.P185Pfs*26. The mutation was verified as a new mutation in the family, and neither parent carried it. The American College of Medical Genetics and Genomics (ACMG) guidelines indicated that this mutation type was a pathogenic mutation. This locus had not been reported in the human gene mutation database (HGMDpro). In addition, c.109 (exon2) G > A (missense mutation) in GJB2 gene was also detected, leading to amino acid change p. V37I. Both parents were carriers in the family verification. According to the ACMG guidelines, this mutation type was a pathogenic mutation. This locus had been reported in HGMDpro database. Conclusion Both Alport syndrome and GJB2 gene mutation can lead to hearing loss. When hearing loss in children with AS, we should not only consider the primary disease, but also be alert to the presence of other comorbidities to avoid missed diagnosis and misdiagnosis.

Key words: Alport syndrome, GJB2, hearing loss