title: A novel C8orf37 splice mutation and genotype-phenotype correlation for cone-rod dystrophy.
abstract: To identify the disease-causing mutation in a consanguineous family of Morrocan origin with syndromic autosomal recessive (ar) cone-rod dystrophy (CRD) in two patients and describe genotype-phenotype correlations.
  
  
  
  Genome-wide homozygosity mapping and direct sequencing of C8orf37, located in a homozygous interval, was performed in the family. mRNA analysis revealed the effect of the newly identified splice-site mutation. For a comparative analysis phenotypic and genetic data of C8orf37 mutations were extracted from published cases.
  
  
  
  The new splice-site mutation c.155+2T>C identified in the family results in a skipping of 82 bp. The CRD phenotypes of our patients were consistent with previous reports. Non-ocular findings in our patients and two previously described patients were postaxial polydactyly present at birth. Both families with additional postaxial polydactyly had splice site mutations affecting intron 1 of C8orf37, one at the slice donor and one at the splice acceptor site.
  
  
  
  This report extends the genotypic spectrum of C8orf37-associated retinal dystrophies and demonstrates for the first time a genotype-phenotype correlation between an arCRD-polydactyly-association and truncating germline mutations affecting the N-terminal region of the protein. Furthermore, our findings underline the ciliary function of C8orf37 protein.
authors: a Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University , Düsseldorf , Germany.
authors: Nils
authors: N
authors: Rahner
authors: b Cologne Center for Genomics (CCG), University of Cologne , Cologne , Germany.
authors: Gudrun
authors: G
authors: Nuernberg
authors: c Medical Faculty, Department of Ophthalmology , Heinrich-Heine University , Düsseldorf , Germany.
authors: David
authors: D
authors: Finis
authors: b Cologne Center for Genomics (CCG), University of Cologne , Cologne , Germany.|d Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne , Germany.|e Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) , University of Cologne , Cologne , Germany.
authors: Peter
authors: P
authors: Nuernberg
authors: a Medical Faculty, Institute of Human Genetics and Anthropology, Heinrich-Heine University , Düsseldorf , Germany.
authors: Brigitte
authors: B
authors: Royer-Pokora
mesh_terms: D000293:Adolescent; D000071700:Cone-Rod Dystrophies / Q000175:diagnosis / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D018095:Germ-Line Mutation; D006801:Humans; D010375:Pedigree; D017689:Polydactyly / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D011506:Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C570604:CFAP418 protein, human
keywords: C8orf37; Ciliopathy; cone-rod dystrophy; genotype-phenotype correlation; postaxial polydactyly