Avtor/Urednik		Gorinšek, Benjamin
Naslov		Genetska analiza Alportovega sindroma v slovenski populaciji
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Univerza v Ljubljani, Medicinska fakulteta
Leto izdaje		2000
Obseg		str. 56
Jezik		slo
Abstrakt		Alport syndrome (AS) is hereditary progressive nephropathy, which is characterized by renal failure accompanied by hematuria and varying degrees of proteinuria, sensorineural deafness, and eye lesions. Carrier females have a variable and generally milder clinical course of disease. In 95% of male patients the disease is characterized by complete renal failure. Pathognomonic findings in glomerular basement membrane (GBM) such as thickening and thinning with splitting of the lamina densa have been revealed at the ultrastructural level. In vast families, AS is inherited as a dominant X-chromosome-linked trait. Mutations in COL4A5 gen (Xq22), which codes for major structural component of GBM - alpha5 chain of collagen IV, have been found in majority (85%) of families with X-chromosome-linked AS . To date, close to 300 different mutations have been identified in COL4A5 gene which appear randomly along the gene. Mutations in COL4A3 and COL4A4 genes, located at 2q35, cause autosomal recesive and dominant type of AS. Approximately 420 bp apart form COL4A5 gene is located COL4A6 gene, which is believed to be involved in aetiology of a rare type of AS companied by diffuse leiomiomatosis. Here, we report the first systematic mutation screening of all 51 exons with boundary intronic sequences of COL4A5 gene by SSCP analysis in 16 randomly collected AS suspected families in slovenian population. Seven different mutations were identified in 8 families by cycle sequencing. A previous described mutation G624D (GGT>GAT) has been identified in two families. We identified seven different mutations, six of them are to the best of our knowlage new: G669R (GGT>CGT), G325R (GGA>CGA), R266X (CGA>TGA), G811R (GGA>AGA), G319D (GGT>GAT) and 1234+17 T del. Intronic mutation 1234+17 T del most likely influences the splicing of mRNA. (Abstract truncated at 2000 characters).
Deskriptorji		NEPHRITIS, HEREDITARY COLLAGEN SLOVENIA EXONS MUTATION LINKAGE (GENETICS) POLYMERASE CHAIN REACTION GENE AMPLIFICATION BASE SEQUENCE POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL NUCLEIC ACID CONFORMATION NUCLEIC ACID HETERODUPLEXES ELECTROPHORESIS, POLYACRYLAMIDE GEL DNA