| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q36.3 | Hematuria, benign familial, 2 | 620320 | Autosomal dominant | 3 | COL4A3 | 120070 |
A number sign (#) is used with this entry because of evidence that benign familial hematuria-2 (BFH2) is caused by heterozygous mutation in the COL4A3 gene (120070) on chromosome 2q36.
Benign familial hematuria (BFH) 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 (see 301050), which results in end-stage renal failure and may be associated with hearing loss and ocular anomalies (review by Lemmink et al. (1996)).
For a discussion of genetic heterogeneity of BFH, see BFH1 (141200).
Badenas et al. (2002) reported 6 unrelated Spanish families with autosomal dominant benign familial hematuria, including 4 families with mutation in the COL4A3 gene. 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.
Lemmink et al. (1996) demonstrated linkage of BFH to the COL4A3 and COL4A4 (120131) genes at chromosome 2q35-q37.
The transmission pattern of BFH in the families reported by Badenas et al. (2002) was consistent with autosomal dominant inheritance.
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; G985V, 120070.0008) and 4 different heterozygous mutations in the COL4A4 gene (see, e.g., 120131.0007 and 120131.0008).
Badenas, C., Praga, M., Tazon, B., Heidet, L., Arrondel, C., Armengol, A., Andres, A., Morales. E., Camacho, J. A., Lens, X., Davila, S., Mila, M., Antignac, C., Darnell, A., Torra, R. Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria. J. Am. Soc. Nephrol. 13: 1248-1254, 2002. [PubMed: 11961012] [Full Text: https://doi.org/10.1681/ASN.V1351248]
Lemmink, H. H., Nillesen, W. N., Mochizuki, T., Schroder, C. H., Brunner, H. G., van Oost, B. A., Monnens, L. A. H., Smeets, H. J. M. Benign familial hematuria due to mutation of the type IV collagen alpha-4 gene. J. Clin. Invest. 98: 1114-1118, 1996. [PubMed: 8787673] [Full Text: https://doi.org/10.1172/JCI118893]