University of Tasmania
Browse

File(s) under permanent embargo

Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci

journal contribution
posted on 2023-05-17, 08:31 authored by Kathryn BurdonKathryn Burdon, Coster, DJ, Jac CharlesworthJac Charlesworth, Mills, RA, Laurie, KJ, Giunta, C, Alexander HewittAlexander Hewitt, Latimer, P, Craig, JE
Keratoconus is a debilitating ocular disease characterised by progressive asymmetrical thinning of the cornea, the clear covering at the front of the eye. The resulting protrusion of the cornea results in severe refractive error, in the most severe cases requiring corneal grafting. It is a complex disease with a genetic component. Despite several reports of linked loci, major gene identification has been elusive. A genome-wide linkage scan in a large Australian pedigree with apparent autosomal dominant keratoconus was conducted using the Affymetrix 10K SNP chip and two regions of linkage identified. Functional candidate genes from within both linkage peaks were assessed for corneal expression and screened for mutations in affected family members. Equal evidence of linkage was detected to both 1p36.23-36.21 and 8q13.1-q21.11 with LOD scores of 1.9. Analysis of both loci concurrently suggests digenic linkage with two-locus LOD score of 3.4. All affected individuals carry identical haplotypes at both loci. Carriers of either linked haplotype without the other do not have keratoconus. No mutations were identified in the following candidate genes expressed in the cornea: ENO1, CTNNBIP1, PLOD1, UBIAD1, SPSB1 or TCEB1. Although the pedigree appears to demonstrate simple autosomal dominant inheritance, the disorder is actually genetically complex. This pedigree may provide a link between inherited forms of keratoconus and sporadic cases.

History

Publication title

Human Genetics

Volume

124

Issue

4

Pagination

379-386

ISSN

0340-6717

Department/School

Menzies Institute for Medical Research

Publisher

Springer-Verlag

Place of publication

175 Fifth Ave, New York, USA, Ny, 10010

Rights statement

Copyright 2008 Springer-Verlag

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

Usage metrics

    University Of Tasmania

    Categories

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC