Autosomal-dominant Alport syndrome: Natural history of a disease due to COL4A3 or COL4A4 gene

Chiara Pescucci, Francesca Mari, Ilaria Longo, Paraskevi Vogiatzi, Rossella Caselli, Elisa Scala, Cataldo Abaterusso, Rosanna Gusmano, Marco Seri, Nunzia Miglietti, Elena Bresin, Alessandra Renieri

Research output: Contribution to journalArticlepeer-review


Background. Alport syndrome is a clinically and genetically heterogeneous nephropathy. The majority of cases are transmitted as an X-linked semidominant condition due to COL4A5 mutations. In this form males are more severely affected than females. Less than 10% of cases are autosomal recessive due to mutation in either COL4A3 or COL4A4. In this rarer form, both males and females are severely affected. Only two cases of autosomal-dominant Alport syndrome have been reported, one due to a COL4A3 mutation and the other due to a COL4A4 mutation. Because of the paucity of the reported families, the natural history of autosomal-dominant Alport syndrome is mostly unknown. Methods. Four families with likely autosomal-dominant Alport syndrome were investigated. COL4A3 and COL4A4 genes were analyzed by denaturing high-performance liquid chromatography (HPLC). Automated sequencing was performed to identify the underlying mutation. Results. Two families had a mutation in the COL4A4 gene and two in the COL4A3. Accurate clinical evaluation of family members showed interesting results. Affected individuals (22 persons) had a wide range of phenotypes from end-stage renal disease (ESRD) in the fifth decade to a nonprogressive isolated microhematuria. Finally, three heterozygous individuals (90, 22 and 11 years old, respectively) were completely asymptomatic. Conclusion. This paper demonstrated that patients affected by autosomal-dominant Alport syndrome have a high clinical variability. Moreover, a reduced penetrance of about 90% (3 of 25) may be considered for the assessment of recurrence risk during genetic counseling of these families.

Original languageEnglish
Pages (from-to)1598-1603
Number of pages6
JournalKidney International
Issue number5
Publication statusPublished - May 2004


  • Autosomal-dominant Alport syndrome
  • Collagen IV genes
  • Incomplete penetrance
  • Inherited nephropathy
  • Phenotypic variability

ASJC Scopus subject areas

  • Nephrology


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