RATIONALE & OBJECTIVE: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS).

STUDY DESIGN: Retrospective cohort study.

SETTING & PARTICIPANTS: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected.

OBSERVATIONS: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P=0.8), causative genes (P=0.6), or type of variant (P=0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was-1.46 (-1.66 to-1.26) mL/min/1.73m2 per year for the overall group, with no significant differences between ADAS genes (P=0.2).

LIMITATIONS: The relatively small size of this series from a single country, potentially limiting generalizability.

CONCLUSIONS: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

Original languageEnglish
Pages (from-to)560-570.e1
JournalAmerican Journal of Kidney Diseases
Issue number4
Publication statusPublished - 1 Apr 2021


  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alport syndrome
  • Autoantigens/genetics
  • COL4A3
  • COL4A4
  • Cohort Studies
  • Collagen Type IV/genetics
  • Female
  • Genetic Testing/methods
  • Genetic Variation/genetics
  • Humans
  • Male
  • Middle Aged
  • Nephritis, Hereditary/diagnosis
  • Renal Insufficiency/diagnosis
  • Retrospective Studies
  • Young Adult
  • autosomal-dominant Alport syndrome
  • familial benign hematuria
  • familial hematuria
  • genetic
  • genotype–phenotype correlation
  • hearing loss
  • hereditary kidney disease
  • inherited kidney disease
  • thin basement membrane disease


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