Universität zu Köln

Weber, Stefanie, Strasser, Katja, Rath, Sabine, Kittke, Achim, Beicht, Sonja, Alberer, Martin, Lange-Sperandio, Baerbel, Hoyer, Peter F., Benz, Marcus R., Ponsel, Sabine, Weber, Lutz T., Klein, Hanns-Georg and Hoefele, Julia ORCID: 0000-0002-7917-7129 (2016). Identification of 47 novel mutations in patients with Alport syndrome and thin basement membrane nephropathy. Pediatr. Nephrol., 31 (6). S. 941 - 956. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Alport syndrome (ATS) is a progressive hereditary nephropathy characterized by hematuria and proteinuria. It can be associated with extrarenal manifestations. In contrast, thin basement membrane nephropathy (TBMN) is characterized by microscopic hematuria, is largely asymptomatic, and is rarely associated with proteinuria and end-stage renal disease. Mutations have been identified in the COL4A5 gene in ATS and in the COL4A3 and COL4A4 genes in ATS and TBMN. To date, more than 1000 different mutations in COL4A5, COL4A3, and COL4A4 are known. In this study mutational analysis by exon sequencing and multiplex ligation-dependent probe amplification was performed in a large European cohort of families with ATS and TBMN. Molecular diagnostic testing of 216 individuals led to the detection of 47 novel mutations, thereby expanding the spectrum of known mutations causing ATS and TBMN by up to 10 and 6 %, respectively, depending on the database. Remarkably, a high number of ATS patients with only single mutations in COL4A3 and COL4A4 were identified. Additionally, three ATS patients presented with synonymous sequence variants that possible affect correct mRNA splicing, as suggested by in silico analysis. The results of this study clearly broaden the genotypic spectrum of known mutations for ATS and TBMN, which will in turn now facilitate future studies into genotype-phenotype correlations. Further studies should also examine the significance of single heterozygous mutations in COL4A3 and COL4A4 and of synonymous sequence variants associated with ATS.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weber, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Strasser, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Rath, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Kittke, Achim UNSPECIFIED UNSPECIFIED UNSPECIFIED Beicht, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Alberer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lange-Sperandio, Baerbel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyer, Peter F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benz, Marcus R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ponsel, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Lutz T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Hanns-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefele, Julia UNSPECIFIED orcid.org/0000-0002-7917-7129 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-274808
DOI:	10.1007/s00467-015-3302-4
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	31
Number:	6
Page Range:	S. 941 - 956
Date:	2016
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GENOTYPE-PHENOTYPE CORRELATIONS; BENIGN FAMILIAL HEMATURIA; COL4A5 COLLAGEN GENE; COL4A3/COL4A4 MUTATIONS; MOLECULAR ANALYSIS; NATURAL-HISTORY; RENAL-FAILURE; PCR; DIAGNOSIS Multiple languages Pediatrics; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27480