Genotype-Phenotype Correlations in Alport Syndrome-A Single-Center Experience

Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD).

This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival.

A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98-54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p < 0.001).

Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.