Familial hematurias: what we know and what we don’t

Abstract

Over the past 30 years we have learned a great deal about the molecular genetics and natural history of familial forms of hematuria. Our enhanced understanding of these conditions has yet to generate effective therapies for Alport syndrome, the form of familial hematuria associated with end-stage renal disease. This review briefly presents the current state of knowledge about familial hematuria and argues for the organization of clinical therapeutic trials in Alport syndrome.

COL4A3/COL4A4 Mutations Producing Focal Segmental Glomerulosclerosis and Renal Failure in Thin Basement Membrane Nephropathy

“…A predominant feature was the significant allelic and phenotypic heterogeneity in the presence also of incomplete penetrance. 2,20,23,24 Of importance is also that TBMN in several reports (reference 21 and references therein) was shown to be associated with other glomerulopathies, such as IgA nephropathy, FSGS, minimalchange disease, mesangioproliferative glomerulonephritis, and others.…”

Thin basement membrane nephropathy: is there genetic predisposition to more severe disease?

“…It should not be a surprise if closer look and improved techniques prove that COL4A3/COL4A4 mutations account for an even higher portion of TBMN cases that presently have been overlooked. The term TBMN, with only few exceptions, has largely been used as a synonym for benign familial microscopic hematuria, which nearly always is the only symptom, with excellent prognosis [1][2][3]. Those few exceptions are worth concentrating on, in view of a recent publication from my laboratory, which provides voluminous exceptional data from a population on the island of Cyprus [4].…”

The Power of Molecular Genetics in Establishing the Diagnosis and Offering Prenatal Testing: The Case for Alport Syndrome

“…According to some older publications, these patients occasionally progress to proteinuria and chronic kidney disease (CKD) while a small percentage reach end-stage kidney disease (ESKD) on long follow-up [5][6][7][8] . In a paper we published in 2007, we presented our initial experience in investigating 116 patients of 13 Cypriot families, where 20 renal biopsies had the dual diagnosis of focal segmental glomerulosclerosis (FSGS) and TBMN.…”