Universität zu Köln

Weber, Stefanie, Buescher, Anja K., Hagmann, Henning, Liebau, Max C., Heberle, Christian, Ludwig, Michael, Rath, Sabine, Alberer, Martin, Beissert, Antje, Zenker, Martin, Hoyer, Peter F., Konrad, Martin, Klein, Hanns-Georg and Hoefele, Julia ORCID: 0000-0002-7917-7129 (2016). Dealing with the incidental finding of secondary variants by the example of SRNS patients undergoing targeted next-generation sequencing. Pediatr. Nephrol., 31 (1). S. 73 - 82. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Steroid-resistant nephrotic syndrome (SRNS) is a severe cause of progressive renal disease. Genetic forms of SRNS can present with autosomal recessive or autosomal dominant inheritance. Recent studies have identified mutations in multiple podocyte genes responsible for SRNS. Improved sequencing methods (next-generation sequencing, NGS) now promise rapid mutational testing of SRNS genes. In the present study, a simultaneous screening of ten SRNS genes in 37 SRNS patients was performed by NGS. In 38 % of the patients, causative mutations in one SRNS gene were found. In 22 % of the patients, in addition to these mutations, a secondary variant in a different gene was identified. This high incidence of accumulating sequence variants was unexpected but, although they might have modifier effects, the pathogenic potential of these additional sequence variants seems unclear so far. The example of molecular diagnostics by NGS in SRNS patients shows that these new sequencing technologies might provide further insight into molecular pathogenicity in genetic disorders but will also generate results, which will be difficult to interpret and complicate genetic counseling. Although NGS promises more frequent identification of disease-causing mutations, the identification of causative mutations, the interpretation of incidental findings and possible pitfalls might pose problems, which hopefully will decrease by further experience and elucidation of molecular interactions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weber, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Buescher, Anja K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebau, Max C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heberle, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludwig, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rath, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Alberer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Beissert, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Zenker, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoyer, Peter F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Konrad, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Hanns-Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoefele, Julia UNSPECIFIED orcid.org/0000-0002-7917-7129 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-293295
DOI:	10.1007/s00467-015-3167-6
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	31
Number:	1
Page Range:	S. 73 - 82
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 CONGENITAL NEPHROTIC SYNDROME; GENOTYPE/PHENOTYPE CORRELATIONS; CLINICAL SPECTRUM; NPHS2 MUTATIONS; NEPHRIN GENE; WT1; PROTEIN; ALPHA-ACTININ-4; CHILDREN; PODOCIN Multiple languages Pediatrics; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29329