We report the first case of an MYH9-RD in a patient of Greek origin presenting with macroscopic hematuria and presenile cataract caused by a p.R1165C mutation.
Pilot study to test the efficacy and safety of activated recombinant factor VII (NovoSeven) in the treatment of refractory hemorrhagic cystitis following high-dose chemotherapy.
In family 2, a novel COL4A3 missense mutation c.G2290A (p.Gly997Glu) was identified in a 45-year-old male diagnosed with focal segmental glomerulosclerosis and was present in all his affected family members, who exhibited disease ranging from isolated microscopic hematuria to end stage renal disease (ESRD).
The major genes involved are the following: (i) the collagen IV genes COL4A3/A4/A5 that are expressed in the glomerular basement membranes (GBM) and are responsible for the most frequent forms of microscopic hematuria, namely Alport syndrome (X-linked or autosomal recessive) and thin basement membrane nephropathy (TBMN).
Heterozygous mutations in the COL4A3/ COL4A4 genes are currently thought to be responsible for familial benign microscopic haematuria and maintenance of normal long-term kidney function.
The families in whom hematuria does not appear to segregate with the COL4A3/COL4A4 locus cannot all be explained by de novo mutations, and nonpenetrant or coincidental hematuria.This suggests a further TBMN locus.
The families in whom hematuria does not appear to segregate with the COL4A3/COL4A4 locus cannot all be explained by de novo mutations, and nonpenetrant or coincidental hematuria.This suggests a further TBMN locus.
We examined 62 unrelated individuals diagnosed with TBMN by renal biopsy (N= 49, 79%) or a positive family history of hematuria but without a biopsy (N= 13, 21%) for mutations in the COL4A3 gene and the COL4A3/COL4A4 promoter.
We examined 62 unrelated individuals diagnosed with TBMN by renal biopsy (N= 49, 79%) or a positive family history of hematuria but without a biopsy (N= 13, 21%) for mutations in the COL4A3 gene and the COL4A3/COL4A4 promoter.
The present study describes molecular changes of the COL4A4 gene that cause both diseases: autosomal recessive AS and BFH in a consanguine family with a 400-year-old history of haematuria.
Families with TBMN in whom hematuria does not segregate with the COL4A3/COL4A4 locus can be explained by de novo mutations, incomplete penetrance of hematuria, coincidental hematuria in family members without COL4A3 or COL4A4 mutations, and by a novel gene locus for TBMN.
Collagen type IV nephropathy is an entity in itself, and phenotypic manifestations of COL4A3/COL4A4 mutations may range from monosymptomatic hematuria (BFH) to severe renal failure (AS), depending on the gene dosage.