Universität zu Köln

Birtel, Johannes, Gliem, Martin, Hess, Kristina, Birtel, Theresa H., Holz, Frank G., Zechner, Ulrich, Bolz, Hanno J. and Herrmann, Philipp (2020). Comprehensive Geno- and Phenotyping in a Complex Pedigree Including Four Different Inherited Retinal Dystrophies. Genes, 11 (2). BASEL: MDPI. ISSN 2073-4425

Full text not available from this repository.

Abstract

Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Birtel, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Gliem, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hess, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Birtel, Theresa H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holz, Frank G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zechner, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Herrmann, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-346190
DOI:	10.3390/genes11020137
Journal or Publication Title:	Genes
Volume:	11
Number:	2
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2073-4425
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DOMINANT RETINITIS-PIGMENTOSA; WAARDENBURG SYNDROME TYPE-2; RHODOPSIN MUTATIONS; CONE; ROD; ABCR; PREVALENCE; LIPOFUSCIN; FAMILIES; SPECTRUM Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34619