HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vieira, H. Articles by Gregory-Evans, C. Y. Search for Related Content PubMed PubMed Citation Articles by Vieira, H. Articles by Gregory-Evans, C. Y.

First Genomic Localization of Oculo-Oto-Dental Syndrome with Linkage To Chromosome 20q13.1

¹ From the Departments of Cell and Molecular Biology and ² Ophthalmology, Faculty of Medicine, Imperial College, London, United Kingdom; and the ³ Department of Medical Genetics, Birmingham Women’s Hospital, Birmingham, United Kingdom.

PURPOSE. To characterize the phenotype of autosomal dominant oculo-oto-dental (OOD) syndrome, map the disease locus in a five-generation British family, and evaluate a candidate gene.

METHODS. Full clinical assessments in all affected patients included slit lamp and retina examination, refraction, A-scan ultrasound, audiograms, and dental assessments. Genomic DNA from all family members was genotyped, by polymerase chain reaction, for polymorphic genetic markers covering the entire genome. Two-point LOD scores were generated using a linkage analysis suite of computer programs. The gene for eyes absent 2 (EYA2) was screened for mutations by direct automated sequencing and Southern blot analysis.

RESULTS. All the affected individuals examined had iris and retina coloboma associated with high-frequency, progressive, sensorineural deafness and globodontia. This is the only genetic disease known to result in pathologically enlarged teeth. The locus for OOD (OOD1) was mapped to 20q13.1. A maximum two-point LOD score of 3.31 was obtained with marker locus D20S836 at a recombination fraction of = 0.00. Two critical recombinations in the pedigree positioned this locus to a region flanked by marker loci D20S108 and D20S159, giving a critical disease interval of 12 centimorgans (cM). Mutation screening of one candidate gene, EYA2, revealed no disease-associated mutations or polymorphic variants.

CONCLUSIONS. This is the first genetic localization for the OOD phenotype (ODD1). The disease-causing gene is localized within a 12-cM critical region of chromosome 20q13.1. The identification of the disease gene is not only relevant to the study of vision and hearing defects, but also highlights an exceptional gene involved in the development of human dentition.

This article has been cited by other articles:

				C. Y. Gregory-Evans, M. Moosajee, M. D. Hodges, D. S. Mackay, L. Game, N. Vargesson, A. Bloch-Zupan, F. Ruschendorf, L. Santos-Pinto, G. Wackens, et al. SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma Hum. Mol. Genet., October 15, 2007; 16(20): 2482 - 2493. [Abstract] [Full Text] [PDF]

				C Y Gregory-Evans, M J Williams, S Halford, and K Gregory-Evans Ocular coloboma: a reassessment in the age of molecular neuroscience J. Med. Genet., December 1, 2004; 41(12): 881 - 891. [Abstract] [Full Text] [PDF]