Abstract We describe a father and three offspring with hematuria. The father and one girl also complained of flank pain. Renal function tests and ophthalmological examinations were normal in all. The father had very mild neural deafness. The renal biopsy samples of two affected siblings showed changes compatible with thin basement membrane disease. Genetic analysis revealed a novel missense mutation in exon 32 of COL4A4 to be responsible for the phenotype in this family. We suggest that thin basement membrane disease may have overlap- ping clinical features with other causes of hematuria; ge- netic analysis may help in the differential diagnosis and help us further understand the disease processes. Keywords Familial benign hematuria · Phenotype · COL4A4 Introduction Familial hematuria was defined in the beginning of this century by Guthrie [1]. Later Alport described a progres- sive familial hematuria associated with deafness in males [2]. Subsequent studies showed Alport syndrome (AS) to be an inherited disease of type IV collagen [3, 4]. With increasing numbers of cases, benign familial hematuria (BFH) was classified as a distinct clinicopathological en- tity with persistent or recurrent hematuria, an autosomal dominant inheritance, and essentially normal renal func- tion [3–8]. Recent reports have shown that both BFH and autosomally inherited AS are linked to the COL 4A3- COL4A4 locus [3, 8–10]. However, not all families with benign familial hematuria are linked to the COL4A3/ COL4A4 locus [11, 12]. Morphologically, BFH is associated with thinning of the glomerular basement membrane (GBM) and has thus also been called “thin basement membrane disease” (TBMD). Clinical evaluation of such cases requires a careful family history to detect the occurrence of renal insufficiency and deafness in relatives, which would sug- gest a clinical diagnosis of AS. We describe here a father and three offspring with this syndrome, compatible with an autosomal dominant in- heritance. A novel mutation in COL4A4 was detected in this family. Case reports The index patient (patient 1, sib 4 in Table 1) was an 11-year-old boy who had presented with microscopic and occasionally macro- scopic episodes of hematuria in the previous 2 years. His past his- tory was unremarkable. Blood pressure and growth were normal. He had nil to mild proteinuria. Renal function tests and intravenous urography were normal (Table 1), as was audiometry. At the same time the 47-year-old father presented to the Depart- ment of Urology because of macroscopic hematuria. Although he had had complaints of occasional flank pain in the previous 20 years, he had never had a urinalysis done. The change in urine color had become very evident in the previous 2–3 years; however, he was not able to comment on for how long he had had “dark urine.” Laborato- ry examination revealed that he had dysmorphic red blood cells in urine, a mild proteinuria of 30 mg/dl and normal creatinine clear- ance. The intravenous pyelography was normal. An audiometric test revealed a very slight high-tone neural deafness on the right side only. Two sisters of the index case, 15 and 18 years old, also had he- maturia. One had severe loin pain during macroscopic attacks. On examination they had normal blood pressure and normal develop- ment. The renal function tests, ultrasonographic examination of the kidneys, and audiometry tests were all within the normal range. The mother and eldest brother were screened and found to S. Ozen ( ✉ ) · N. Besbas · A. Bakkaoglu Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey e-mail: sozen@gen.hun.edu.tr Fax: +90-312-4424136 D. Ertoy Department of Pathology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey L. Heidet · L. Cohen-Solal · C. Antignac INSERM U423, University Rene Descartes, Ho ˆpital Necker-Enfants Malades, Paris, France H. Ozen Department of Urology, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey Pediatr Nephrol (2001) 16:874–877 © IPNA 2001 GENETIC RENAL DISEASE / ORIGINAL ARTICLE Seza Ozen · Dilek Ertoy · Laurence Heidet Loal Cohen-Solal · Haluk Ozen · Nesrin Besbas Aysin Bakkaoglu · Corinne Antignac Benign familial hematuria associated with a novel COL4A4 mutation Received: 29 January 2001 / Revised: 5 June 2001 / Accepted: 6 June 2001