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.


OBJECTIVE
To describe a family of Iraqi Jewish origin, several of whose members suffer from non-syndromic renal failure without deafness or ocular defects and where transmission is by autosomal dominant inheritance. We present the case histories of four family members and describe the molecular analysis performed in order to seek a possible linkage to one of the genes causing 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 Alport and Alport-like syndromes.


RESULTS
Histology of the renal biopsy specimens showed non-specific findings. 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 nephritis, characterized by hypertension and progressive renal failure without significant hematuria or proteinuria. The main histological changes are non-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 the basic defect in this type of nephritis.
Ilan
T
T
Department of Pediatric Hematology and Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Shohat
T
T
Tobar
A
A
Magal
N
N
Yahav
M
M
Halpern
G J
GJ
Rechavi
G
G
Shohat
M
M
D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000097:blood; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009394:Nephritis, Hereditary / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics
D003404:Creatinine