Autosomal dominant nephritis with renal failure of non-alport type: Clinical and molecular studies

Background: Familial nephritis is a heterogeneous group of disorders caused by several genetic conditions such as Alport syndrome, glomerulonephritic syndromes, and unclassified nephritis without deafness or ocular defects. Objectives: To describe a family of Iraqi Jewish origin, several of whose m embers suffer from non-syndromic renal failure without deafness or ocular d efects and where transmission is by autosomal dominant inheritance. We pres ent the case histories of four family members and describe the molecular an alysis performed in order to seek a possible linkage to one of the genes ca using Alport or Alport-like syndromes. Methods: We investigated all family members over the age of 18 for evidence of renal failure. We also extracted DNA and carried out molecular linkage analysis with polymorphic markers in each of the known loci involved in Alp ort and Alport-like syndromes. Results: Histology of the renal biopsy specimens showed non-specific findin gs. Linkage was excluded for all the Alport and Alport-like syndrome loci. Conclusions: The condition suffered by several members of this family seems to represent a unique autosomal dominant type of progressive hereditary ne phritis, characterized by hypertension and progressive renal failure withou t significant hematuria or proteinuria. The main histological changes are n on-specific In the early stage of the disease. Our study rules out all the currently known genes that cause Alport syndrome as being responsible for t he basic defect in this type of nephritis.