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G.L. Wang, M.A. Pisacano, S. Lauer, C. Wertenbaker, A. Shanske; Deletion Mapping in a Patient with Del(18)(p11.2p11.3) and Blepharospasm Narrows the Region for a Novel Locus for Inherited Myoclonus-dystonia . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1942.
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Purpose: We present a patient with inherited myoclonus-dystonia with a narrow intrachromosomal deletion of 18p mapping to a novel locus for this disorder. Methods: Case report. AT is 30 yo who presented with eyelid and lower facial spasms. Ten months after the onset of blepharospasms, he developed other involuntary movements including occasional turning of the neck, dystonic movements of the arms, and intermittent grunting resulting from diaphragmatic spasms. Physical exam reveals a short dysmorpic male with craniofacial features including low-set pinna, webbed neck, hypertlorism, micrognathia, large cranium, low nasal bridge, and multiple carious teeth. He also had bilateral gynecomastia and brachydactyly of all digits. Patient underwent botulinum injections and bilateral myomectomies with minimal relief of blepharospasm. Results: Chromosomal analysis of peripheral leukocyte revealed an abnormal male karyotype 46,XY,del(18)(p11.2p11.3). Parental karyotypes were requested, but only a maternal sample was available which was normal. FISH probes using WCP 18 and 18p telomeric probes confirmed the deletion observed by high resolution banding. MRI of the head showed multiple foci of increased signal on T2 in centrum semiovale. Conclusion: Genetic basis for essential blepharospasm has been associated with allele 2 of the dinucleotide repeat in the dopamine receptor DRD5 gene (Misbahuddin et al. 2002). Blepharospasm may also be seen as part of the inherited myoclonus-dystonia disorder (IMD)(MIM159900) associated with the DYT7 gene. Leube et al (1996), localized the DYT7 gene to the short arm of chromosome 18. Using microsatellites from the original 30 cM DYT7 candidate gene region on 18p, they were able to reduce the DYT7 candidate region to a 4.4 cM region around microsatellite D18S1098 at band 18p11.31 between 1.2 and 3.2 cM from the centromere. Grimes et al (2002), using haplotype analysis, demonstrated a common haplotype exist in IMD patients between markers D18S1132 and D18S843, a span of 16.9 cM. We have described a patient with a deletion of only 12 cM in the region of 18p11.2 to 18p11.3 encompassing the DYT7 gene. From a literature search, the locus for IMD has never been localized to such a narrow band on 18p. A long term cell culture will be established from our patient. DNA will be extracted from whole blood and genotyping will be performed using standard PCR protocols with markers covering the deleted area. Cloning of the breakpoint area of our patient will help identify the gene on 18p associated with IMD.
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