Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to Xp22.3

PURPOSE: There is an ongoing discussion whether Lisch corneal dystrophy (ba nd-shaped and whorled microcystic dystrophy of the corneal epithelium) repr esents a disorder that is different from Meesmann corneal dystrophy. The pu rpose of this study was to evaluate at the molecular level if Lisch and Mee smann corneal dystrophies are genetically distinct. METHODS: We examined at the slit lamp a total of 48 members of a family wit h an aggregation of Lisch corneal dystrophy. Genomic DNA was extracted from leukocytes of the peripheral blood of seven affected and six unaffected me mbers of this family. Mutational hotspots in the cornea-specific keratin ge nes K3 and K12 were scanned for mutations by single-strand conformation ana lysis. To test for linkage to the keratin K3 or K12 loci or for X-chromosom al inheritance, six (K3) and four (K12) microsatellite markers each flankin g the keratin loci as well as 22 microsatellite markers covering the X-chro mosome were typed. Linkage was analyzed using the MLINK and FASTMAP procedu res. RESULTS: A total of 19 trait carriers were identified in six generations of the family. No hereditary transmission from father to son was observed. Li nkage was excluded for the keratin K3 and K12 genes. Furthermore, single-st rand conformation analysis detected no mutations in these genes. Multipoint linkage analysis revealed linkage with a maximum likelihood of the odds (L OD) score of 2.93 at Xp22.3, Linkage was excluded for Xp22.2 to Xqter. CONCLUSIONS: Lisch corneal dystrophy is genetically different from Meesmann corneal dystrophy. Evidence was found for linkage of the gene for Lisch co rneal dystrophy to Xp22.3. (C) 2000 by Elsevier Science Inc. All rights res erved.