title: R124C mutation of the betaIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1.
abstract: Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the betaIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the betaIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the betaIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Lübeck, Deutschland. hellenbroich@gmx.de
authors.forename: Y
authors.initials: Y
authors.lastname: Hellenbroich
authors.forename: G
authors.initials: G
authors.lastname: Tzivras
authors.forename: B
authors.initials: B
authors.lastname: Neppert
authors.forename: E
authors.initials: E
authors.lastname: Schwinger
authors.forename: C
authors.initials: C
authors.lastname: Zühlke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000032:analysis; D016326:Extracellular Matrix Proteins; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein