PURPOSE: The estimated world-wide prevalence of keratoconus is 50 to 230 per 100,000 in the general population. Sporadic keratoconus is the leading cause of corneal transplantation surgery in Western countries. Positive family history has been reported in 6% to 8% of patients. The purpose of this study was to map the disease locus in 20 Finnish families with autosomal dominant keratoconus, each family having two or more affected members and with no other associated genetic disease. METHODS: DNA was extracted from blood samples, collected from 42 affected and 34 unaffected family members. Genomic DNA from patients and their parents, was typed for alleles of 292 polymorphic markers. A genome-wide screening was performed to localize the disease gene. Fluorescent markers were amplified by polymerase chain reaction and separated on an automated sequencer. Allele sizes were assigned to each family member, after which LOD scores were calculated. RESULTS: The disease locus was mapped to chromosome 16q, between the markers D16S2624 and D16S3090, with a maximum parametric multipoint LOD score of 4.10 and corresponding nonparametric score of 3.27 (NPL, P = 0.00006). Evidence from 20 families provided support for the linkage, consistent with a single locus for familial autosomal dominant keratoconus without heterogeneity. CONCLUSIONS: This study is the first genome-wide linkage study to map the keratoconus gene. The results suggest that the causative gene in keratoconus is located within the 16q22.3-q23.1 chromosomal region.
PURPOSE: The estimated world-wide prevalence of keratoconus is 50 to 230 per 100,000 in the general population. Sporadic keratoconus is the leading cause of corneal transplantation surgery in Western countries. Positive family history has been reported in 6% to 8% of patients. The purpose of this study was to map the disease locus in 20 Finnish families with autosomal dominant keratoconus, each family having two or more affected members and with no other associated genetic disease. METHODS: DNA was extracted from blood samples, collected from 42 affected and 34 unaffected family members. Genomic DNA from patients and their parents, was typed for alleles of 292 polymorphic markers. A genome-wide screening was performed to localize the disease gene. Fluorescent markers were amplified by polymerase chain reaction and separated on an automated sequencer. Allele sizes were assigned to each family member, after which LOD scores were calculated. RESULTS: The disease locus was mapped to chromosome 16q, between the markers D16S2624 and D16S3090, with a maximum parametric multipoint LOD score of 4.10 and corresponding nonparametric score of 3.27 (NPL, P = 0.00006). Evidence from 20 families provided support for the linkage, consistent with a single locus for familial autosomal dominant keratoconus without heterogeneity. CONCLUSIONS: This study is the first genome-wide linkage study to map the keratoconus gene. The results suggest that the causative gene in keratoconus is located within the 16q22.3-q23.1 chromosomal region.
Authors: Megan Ulmer; Jun Li; Brian L Yaspan; Ayse Bilge Ozel; Julia E Richards; Sayoko E Moroi; Felicia Hawthorne; Donald L Budenz; David S Friedman; Douglas Gaasterland; Jonathan Haines; Jae H Kang; Richard Lee; Paul Lichter; Yutao Liu; Louis R Pasquale; Margaret Pericak-Vance; Anthony Realini; Joel S Schuman; Kuldev Singh; Douglas Vollrath; Robert Weinreb; Gadi Wollstein; Donald J Zack; Kang Zhang; Terri Young; R Rand Allingham; Janey L Wiggs; Allison Ashley-Koch; Michael A Hauser Journal: Invest Ophthalmol Vis Sci Date: 2012-07-03 Impact factor: 4.799
Authors: Xiaohui Li; Yelena Bykhovskaya; Talin Haritunians; David Siscovick; Anthony Aldave; Loretta Szczotka-Flynn; Sudha K Iyengar; Jerome I Rotter; Kent D Taylor; Yaron S Rabinowitz Journal: Hum Mol Genet Date: 2011-10-06 Impact factor: 6.150
Authors: Kathryn P Burdon; Stuart Macgregor; Yelena Bykhovskaya; Sharhbanou Javadiyan; Xiaohui Li; Kate J Laurie; Dorota Muszynska; Richard Lindsay; Judith Lechner; Talin Haritunians; Anjali K Henders; Durga Dash; David Siscovick; Seema Anand; Anthony Aldave; Douglas J Coster; Loretta Szczotka-Flynn; Richard A Mills; Sudha K Iyengar; Kent D Taylor; Tony Phillips; Grant W Montgomery; Jerome I Rotter; Alex W Hewitt; Shiwani Sharma; Yaron S Rabinowitz; Colin Willoughby; Jamie E Craig Journal: Invest Ophthalmol Vis Sci Date: 2011-10-31 Impact factor: 4.799
Authors: Kathryn P Burdon; Douglas J Coster; Jac C Charlesworth; Richard A Mills; Kate J Laurie; Cecilia Giunta; Alex W Hewitt; Paul Latimer; Jamie E Craig Journal: Hum Genet Date: 2008-09-05 Impact factor: 4.132