Linkage of late-onset fuchs corneal dystrophy to a novel locus at 13pTel-13q12.13

Olof H. Sundin, Albert S. Jun, Karl W. Broman, Sammy H. Liu, Siobhan E. Sheehan, Elizabeth C.L. Vito, Walter J. Stark, John D. Gottsch

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE. To identify the gene locus underlying the inheritance of late-onset Fuchs corneal dystrophy (FCD) in a large white kindred. METHODS. Genotypes of small tandem repeat polymorphisms were obtained from 17 affected and 3 unaffected family members, followed by genetic linkage analysis. RESULTS. In this family, classic late-onset FCD appeared to be inherited as a single, dominant Mendelian trait. In two exceptional sibships, however, children aged 10 and 13 years had FCD. In each sibship, both parents were found to be affected, opening the possibility that this unusually early age of onset was the result of homozygosity for an FCD mutation. Genotype results, however, were not consistent with consanguinity of the parents, who appear to have independent cases of FCD. A whole-genome linkage scan mapped FCD to a single locus at 13pTel-13q12.13, with significant two-point LOD scores of 3.91 at D13S1236 and 3.80 at D13S1304. The 26.4-Mb disease interval contains the chromosome 13 nucleolus organizer (RNR1), the centromere, and 44 annotated protein-encoding genes. So far, exons of 10 of these genes have been screened, but no mutations have been found. CONCLUSIONS. FCD1 is the first genetic locus to be identified for late-onset FCD, a common disease of the aging cornea. The exceptional early onset of the disease observed in two children is unusual and might be the result of digenic interaction between FCD1 and an independent late-onset FCD mutation.

Original languageEnglish (US)
Pages (from-to)140-145
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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