Thin basement membrane disease pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Physiology
Glomerular Basement membrane consists of laminin, Type 4 collagen, heparan sulfate proteoglycan and nidogen. Type 4 collagen is generally composed of Gly-X-Y amino acids rich in six alpha chains (alpha 1-6) that gives type 4 collagen a trimeric shape. The nascent GBM is made up of alpha 1 and 2 initially, then alpha 3-4 trimers are secreted after glomerular capillaries formation which becomes the major component of type 4 collagen and giving the GBM its stability.[1]
Pathology
Heterozygous mutation in COL4A3 and COL4A4 gene is responsible for causing autosomal dominant pattern of 40-50% of Thin basement membrane disease in which people have defective alpha 3, alpha 4 , alpha 5 chains. [1] And heterozygous mutation in COL4A5 gene in X-chromosome may cause Thin basement mamebrane disease in female.
Genetics
Thin basement membrane disease is an inherited pattern disease affecting successive generations. It may be due to-
- Autosomal dominant inheritance due to heterozygous mutation in COL4A3 and COL4A4 gene
- Heterozygous mutation in COL4A5 gene in X-chromosome causing Thin basement membrane like disease in female
- 'De novo' mutation.[2]
Associated condition
Condition associated with Thin basement membrane disease include:
- Alport syndrome
Alport syndrome is caused by homozygous or heterozygous mutation of both or either COL4A3, COL4A4 and COL4A5 gene, thus 36% of cases of TBMN with COL4A3, COL4A4 mutation are shown to be associated with Alport Syndrome.[3]
Gross pathology Microscopic pathology
References
- ↑ 1.0 1.1 Miner JH (May 2012). "The glomerular basement membrane". Exp. Cell Res. 318 (9): 973–8. doi:10.1016/j.yexcr.2012.02.031. PMC 3334451. PMID 22410250.
- ↑ Rana K, Wang YY, Buzza M, Tonna S, Zhang KW, Lin T, Sin L, Padavarat S, Savige J (May 2005). "The genetics of thin basement membrane nephropathy". Semin. Nephrol. 25 (3): 163–70. doi:10.1016/j.semnephrol.2005.01.008. PMID 15880327.
- ↑ Buzza M, Wilson D, Savige J (May 2001). "Segregation of hematuria in thin basement membrane disease with haplotypes at the loci for Alport syndrome". Kidney Int. 59 (5): 1670–6. doi:10.1046/j.1523-1755.2001.0590051670.x. PMID 11318937.