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A locus for autosomal dominant keratoconus maps to human chromosome 3p14–q13
  1. F Brancati1,2,
  2. E M Valente1,
  3. A Sarkozy1,2,
  4. J Fehèr3,
  5. M Castori1,2,
  6. P Del Duca4,
  7. R Mingarelli1,
  8. A Pizzuti1,2,
  9. B Dallapiccola1,2
  1. 1CSS Hospital, IRCCS, San Giovanni Rotondo and CSS-Mendel Institute, Rome, Italy
  2. 2Department of Experimental Medicine and Pathology, University “La Sapienza,” Rome, Italy
  3. 3Department of Ophthalmology, University “La Sapienza,” Rome, Italy
  4. 4UO Internal Medicine, POC, Montefiascone, Viterbo, Italy
  1. Correspondence to:
 Dr A Pizzuti
 CSS. Mendel Institute, Viale Regina Margherita 261, I-00198 Rome, Italy;

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Keratoconus (OMIM148300) is a bilateral, non-inflammatory, slowly progressive, corneal ectasia that is a major cause of corneal transplant. Characteristically, the cornea becomes thin and conical, with myopia and irregular astigmatism that leads to vision impairment. The incidence of keratoconus is between 50 and 230 per 100 000, with remarkable differences between ethnic groups.1 Although the pathogenesis of keratoconus still is unknown, little doubt exists about an underlying genetic background. A positive family history is found in 6–8% of patients with keratoconus, and concordance is high among monozygotic twins.1,2 In rare instances, keratoconus is inherited either as a mendelian trait or is associated with a genetic disorder (for example, Down syndrome, Leber’s amaurosis, or connective tissue diseases). For most patients, however, the disease is sporadic.3 The lack of multiple familial cases is a major obstacle to linkage analysis. To date, three loci have been associated with keratoconus, none of them through a genomewide search in a single informative family. A putative 6.8 cM locus was identified in a family affected by keratoconus by direct scan of chromosome 21 only, while an association at 20q12 was found in seven related Tasmanian patients.4,5 More recently, a non-parametric linkage analysis in 20 Finnish small pedigrees with autosomal dominant keratoconus identified a third locus to chromosome 16q.6 Finally, two distinct heterozygous mutations in the VSX1 homeobox gene were identified with a candidate gene approach in two families affected by keratoconus.7

Recent advances in computerised topographic diagnostic techniques enable higher accuracy in the diagnosis of keratoconus, including forme fruste, which eases the identification of extensive families affected by keratoconus. We describe an Italian family with autosomal dominant pure keratoconus and the localisation of a novel keratoconus locus to chromosome 3p14–q13.


Clinical studies

We identified an Italian pedigree with autosomal …

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