Abstract
Gene mutations in COL4A5 located on Xq22 are believed to cause X-linked Alport syndrome, whereas mutations in COL4A3 and COL4A4 located on chromosome 2 are associated with autosomal inherited Alport syndrome or benign familial hematuria. A family with benign familial hematuria caused by COL4A5 mutation, implying X-linked transmission, is reported here for the first time. This result suggests that COL4A5 should be added to the list of causative genes for benign familial hematuria, although the mechanism(s) by which the same mutation leads to the distinct phenotypes, i.e. X-linked Alport syndrome or benign familial hematuria, remains unknown.
References
Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003) Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med 348:2543–2556
Pierides A, Voskarides K, Athanasiou Y, Ioannou K, Damianou L, Arsali M, Zavros M, Pierides M, Vargemezis V, Patsias C, Zouvani I, Elia A, Kyriacou K, Deltas C (2009) Clinico-pathological correlations in 127 patients in 11 large pedigrees, segregating one of three heterozygous mutations in the COL4A3/COL4A4 genes associated with familial haematuria and significant late progression to proteinuria and chronic kidney disease from focal segmental glomerulosclerosis. Nephrol Dial Transplant 24:2721–2729
Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, Meglic A, Jaksa I, Furlan P, Gregoric A, Kaplan-Pavlovcic S, Ravnik-Glavac M, Glavac D (2007) Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int 71:1287–1295
Knebelmann B, Breillat C, Forestier L, Arrondel C, Jacassier D, Giatras I, Drouot L, Deschênes G, Grünfeld JP, Broyer M, Gubler MC, Antignac C (1996) Spectrum of mutations in the COL4A5 collagen gene in X-linked Alport syndrome. Am J Hum Genet 59:1221–1232
Barker DF, Denison JC, Atkin CL, Gregory MC (2001) Efficient detection of Alport syndrome COL4A5 mutations with multiplex genomic PCR-SSCP. Am J Med Genet 98:148–160
Takemura T, Yanagida H, Yagi K, Moriwaki K, Okada M (2003) Alport syndrome and benign familial hematuria (thin basement membrane disease) in two brothers of a family with hematuria. Clin Nephrol 60:195–200
Lemmink HH, Nillesen WN, Mochizuki T, Schröder CH, Brunner HG, van Oost BA, Monnens LA, Smeets HJ (1996) Benign familial hematuria due to mutation of the type IV collagen α4 gene. J Clin Invest 98:1114–1118
Tryggvason K, Patrakka J (2006) Thin basement membrane nephropathy. J Am Soc Nephrol 17:813–822
Badenas C, Praga M, Tazón B, Heidet L, Arrondel C, Armengol A, Andrés A, Morales E, Camacho JA, Lens X, Dávila S, Milà M, Antignac C, Darnell A, Torra R (2002) Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 13:1248–1254
Rana K, Tonna S, Wang YY, Sin L, Lin T, Shaw E, Mookerjee I, Savige J (2007) Nine novel COL4A3 and COL4A4 mutations and polymorphisms identified in inherited membrane diseases. Pediatr Nephrol 22:652–657
Patey-Mariaud de Serre N, Garfa M, Bessiéres B, Noël LH, Knebelmann B (2007) Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients. Kidney Int 72:512–516
Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M (2002) Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant 17:1218–1227
Plant KE, Boye E, Green PM, Vetrie D, Flinter FA (2000) Somatic mosaicism associated with a mild Alport syndrome phenotype. J Med Genet 37:238–239
Krol RP, Nozu K, Nakanishi K, Iijima K, Takeshima Y, Fu XJ, Nozu Y, Kaito H, Kanda K, Matsuo M, Yoshikawa N (2008) Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome. Nephrol Dial Transplant 23:2525–2530
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This study was partly supported by the Mami Mizutani Foundation and Hyogo Prefecture Health Promotion Association.
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Kaneko, K., Tanaka, S., Hasui, M. et al. A family with X-linked benign familial hematuria. Pediatr Nephrol 25, 545–548 (2010). https://doi.org/10.1007/s00467-009-1370-z
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DOI: https://doi.org/10.1007/s00467-009-1370-z