Author/Editor		Petruševska, Gordana; Jovanovič, Rubens; Kostadinova-Kunovska, Slavica; Grcevska, Ladislava; Žižek, Teofil; Boštjančič, Emanuela; Berginc, Gašper; Glavač, Damjan
Title		Genetic studies in patients with hereditary nephritis involving Alport syndrome in Macedonia
Translated title		Genetska preiskava bolnikov z dednim nefritisom vključno z Alportovim sindromom v Makedoniji
Type		članek
Source		In: Luzar B, Poljak M, Glavač D, et al, editors. Molekularna diagnostika v medicini. Zbornik 15. spominsko srečanje akademika Janeza Milčinskega, 36. memorialni sestanek profesorja Janeza Plečnika, 1. srečanje Slovenskega društva za humano genetiko z mednarodno udeležbo; 2005 30 nov - 2 dec; Ljubljana. Ljubljana: Medicinska fakulteta,
Publication year		2005
Volume		str. 207-12
Language		eng
Abstract		Hereditary nephritis Alport syndrome (AS) is a progressive, hematuric glomerulonephritis often associated with sensoneural hearing loss and specific eye lesions, characterized by ultrastructural lesions of the glomerular basement membrane. Ultrastructural analysis shows irregular thickening and splitting of the GBM. This has led to a suggestion that there may be a defect in an important structural element, possibly type IV collagen, which is the major GBM structural component. The predominant farm of Alport syndrome, accounting for about 85% of Alport families, is X-linked; more than 160 different mutations have so tar been identified in the type IV collagen alpha 5 chain (COL4A5) gene, located at Xq22-24 head to head to the COL4A6 gene. However, up to 15% of AS cases are autosomally inherited and are thought to be due to mutations in the COL4A3 and COL4A4 genes, which are located on chromosome 2. We analyzed DNA samples from 17 Macedonian patients (from 16 unrelated families) with diagnosed hereditary nephritis, searching for mutations in the COL IVA5 gene. Analysis consisted of PCR amplification of all 51 exons, followed by Single Strand Conformation Polymorphism (SSCP) analysis by means of acrylamide gel electrophoresis, with subsequent sequencing of the exons showing differing SSCP patterns. SSCP analysis showed that 5 of the patients (from 4 different families) expressed unusual SSCP patterns in more than one exon, and two of the patients had SSC polymorphisms in one exon. Samples from the remaining 10 patients showed no SSCP. Subsequent sequencing of the targeted samples identified 2 different mutations (exons 30 and 25) in 4 patients, 2 of which were mother and daughter.
Descriptors		NEPHRITIS, HEREDITARY POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL MACEDONIA (REPUBLIC)