Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Thin Basement Membrane Nephropathy (TBMN) [N02.9]

OMIM numbers: 141200, 120070 (COL4A3), 120131 (COL4A4)

PD Dr. med. Julia Höfele

Scientific Background

Thin basement membrane nephropathy (TBMN) also known as benign familial hematuria (BFH), is found in about 1% of the population and is characterized by a persistent glomerular hematuria, mild proteinuria, and normal renal function. It is inherited in an autosomal dominant pattern with causative mutations found in the COL4A3 and COL4A4 gene. Alport syndrome (ATS), which manifests as glomerular hematuria and progressive proteinuria resulting in end-stage renal disease, is also caused by mutations in the genes COL4A3 and COL4A4 (autosomal recessive and autosomal dominant inheritance) as well as by mutations in the COL4A5 gene (X-chromosomal inheritance). ATS can be associated with extrarenal manifestations such as sensorineural hearing loss and ocular abnormalities (anterior lenticonus). Since for TBMN and autosomal forms of ATS mutations in the genes COL4A3 and COL4A4 were identififed, patients with TBMN are considered carriers for autosomal recessive ATS. So far only a few mutations are known to cause TBMN or autosomal ATS. Therefore, kidney biopsy still plays an essential role in the differentiation of these entities, although in early stages of ATS a histological differentiation is often not yet possible. Offspring whose parents are both carriers of a heterozygous mutation in the COL4A3 or COL4A4 gene have a chance of 25% to inherit both mutations and develop Alport syndrome. Therefore, if TBMN is present, heterozygosity for the autosomal recessive form of ATS can be assumed.