title: A novel large in-frame deletion within the CACNA1F gene associates with a cone-rod dystrophy 3-like phenotype.
abstract: Cone-rod dystrophies (CORDs) represent a heterogeneous group of monogenic diseases leading to early impairment of vision. The majority of CORD entities show autosomal modes of inheritance and X-linked traits are comparably rare. So far, three X-chromosomal entities were reported (CORDX1, -X2 and -X3). In this study, we analysed a large family of German origin with solely affected males over three generations showing a CORDX-like phenotype. Due to the heterogeneity of cone-rod dystrophies, we performed a combined linkage and X-exome sequencing approach and identified a novel large intragenic in-frame deletion encompassing exons 18 to 26 within the CACNA1F gene. CACNA1F is described causative for CORDX3 in a single family originating from Finland and alterations in this gene have not yet been reported in other CORDX pedigrees. Our data independently confirm CACNA1F as the causative gene for CORDX3-like phenotypes and detailed clinical characterization of the family expands the knowledge about the phenotypic spectrum of deleterious CACNA1F alterations.
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany ; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany ; Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hauke
authors.forename: Andrea
authors.initials: A
authors.lastname: Schild
authors.forename: Antje
authors.initials: A
authors.lastname: Neugebauer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lappa
authors.forename: Julia
authors.initials: J
authors.lastname: Fricke
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rösler
authors.forename: Andrea
authors.initials: A
authors.lastname: Pannes
authors.forename: Dirk
authors.initials: D
authors.lastname: Zarrinnam
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.forename: Susanne
authors.initials: S
authors.lastname: Motameny
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nürnberg
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Eric
authors.initials: E
authors.lastname: Hahnen
authors.forename: Bodo B
authors.initials: BB
authors.lastname: Beck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019721:Ophthalmoscopes; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C113330:CACNA1F protein, human; D020746:Calcium Channels, L-Type