A novel large in-frame deletion within the CACNA1F gene associates with a cone-rod dystrophy 3-like phenotype

PLoS One. 2013 Oct 4;8(10):e76414. doi: 10.1371/journal.pone.0076414. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Calcium Channels, L-Type / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Exome
  • Genetic Association Studies*
  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Linkage
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Ophthalmoscopes
  • Pedigree
  • Phenotype*
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics*
  • Tomography, Optical Coherence
  • Young Adult

Substances

  • CACNA1F protein, human
  • Calcium Channels, L-Type

Supplementary concepts

  • Cone-Rod Dystrophy, X-Linked, 3

Grants and funding

This study was kindly supported by the ´Gertrud Kusen-Stiftung´ (to EH, BB, AS, and AN). JH was supported by the ´Ernst und Berta Grimmke-Stiftung´ (grant 5/10), the ´Köln Fortune Programm´ (grant 46/2010) and the ´Imhoff Stiftung´. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.