Benign familial hematuria is an autosomal dominant condition manifest as nonprogressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane (GBM), and can be considered the ... Benign familial hematuria is an autosomal dominant condition manifest as nonprogressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane (GBM), and can be considered the mildest end of the spectrum of renal diseases due to type IV collagen defects of the basement membrane. The most severe end of the spectrum is represented by Alport syndrome (301050; 203780, 104200), which results in end-stage renal failure and may be associated with hearing loss and ocular anomalies (review by Lemmink et al. (1996)).
McConville et al. (1966) described dominant inheritance of benign familial hematuria. A chemical test for hematuria, paper strips impregnated at one end with orthotoluidine which in the presence of hemoglobin is oxidized to yield a blue color, was ... McConville et al. (1966) described dominant inheritance of benign familial hematuria. A chemical test for hematuria, paper strips impregnated at one end with orthotoluidine which in the presence of hemoglobin is oxidized to yield a blue color, was used for diagnosis. Earlier reports have also referred to this condition (e.g., Livaditis and Ericsson, 1962; Ayoub and Vernier, 1965). Lemmink et al. (1996) reported a large family with BFH spanning 3 generations. The index patient, a member of the third generation, presented with hematuria at the age of 5 years. He was found to carry a heterozygous mutation in the COL4A4 gene (120131.0003). Family history was negative for renal failure and deafness. Electron microscopy of a renal biopsy specimen from the proband showed regions with malformations of the GBM typical for Alport syndrome and regions that were thin. Microscopic hematuria was present in many relatives, including the 75-year-old paternal grandfather who had a normal serum creatinine concentration, indicating normal renal function. The family was complicated by the fact that the mother of the index case also had microscopic hematuria as did many of her relatives, although she did not have an identifiable mutation. The index patient, 16 years old at the time of the report, had developed proteinuria and may have inherited a COL4A4 gene mutation from both parents. Lemmink et al. (1996) speculated that the presence of 2 mutations might account for the severe histologic changes in the GBM in the proband. Badenas et al. (2002) reported 6 unrelated Spanish families with autosomal dominant benign familial hematuria. All had persistent or recurrent microscopic hematuria not associated with other abnormalities such as renal failure or deafness. At least 1 member of each family had undergone a renal biopsy with ultrastructural examination showing a thin glomerular basement membrane. None developed proteinuria.
In affected members of a large family segregating BFH, Lemmink et al. (1996) identified a heterozygous mutation in the COL4A4 gene (G897E; 120131.0003).
In affected members of 6 (60%) of 10 unrelated Spanish families with benign ... In affected members of a large family segregating BFH, Lemmink et al. (1996) identified a heterozygous mutation in the COL4A4 gene (G897E; 120131.0003). In affected members of 6 (60%) of 10 unrelated Spanish families with benign familial hematuria, Badenas et al. (2002) identified 2 different heterozygous mutations in the COL4A3 gene: G1015E (120070.0007) and G985V (120070.0008) and 4 different heterozygous mutations in the COL4A4 gene (see, e.g., 120131.0007 and 120131.0008).