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HM Vieira, N Lim, JL Brookes, LA Brueton, K Gregory-Evans, CY Gregory-Evans; Oculo-oto-dental Syndrome: Linkage to 20q13.1 . Invest. Ophthalmol. Vis. Sci. 2002;43(13):824.
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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 for polymorphic genetic markers covering the entire genome, using polymerase chain reaction. Two-point LOD scores were generated using the linkage analysis suite of 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 had iris and retina coloboma associated with high frequency, progressive, sensorineural deafness and globodontia. It 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 recombination fraction of theta = 0.00. Two critical recombinations in the pedigree positioned this locus to a region flanked by marker loci D20S108 and D20S159, giving a probable critical disease interval of 7 cM. Mutation screening of one candidate gene, EYA2, revealed no disease-associated mutations or polymorphic variants. Conclusion:This is the first genetic localization for the OOD phenotype (ODD1). The disease-causing gene is localized within a 7cM critical region of chromosome 20q13.1. Identification of the causative gene is critical to complete understanding of the neurological pathology and the development of human dentition.
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