Recurrent genomic mutation 507delT in three Lipoid Proteinosis (Urbach-Wiethe) pedigrees from central Iran. L. Youssefian1, H. Vahidnezhad1,2, M. Daneshpazhooh3, S. Abdollahzadeh4, H. Talari5, C. Chams-Davatchi3, S. Akhondzadeh6, R. Mobasher3, M. Tabrizi1 1) Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Tehran, Iran; 2) Molecular Medicine Division, Biotechnology Research center, Pasteur institute of Iran, Tehran, Iran; 3) Department of Dermatology, Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran; 4) Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; 5) Radiology Department and Anatomic Science Research Center, Kashan University of Medical Sciences,Kashan, Iran; 6) Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

   Lipoid proteinosis reports from Iran are rare. Recently, a mutation has been reported from Iran. We aimed to collect and analyze a large number of individuals in affected families and conduct genetic testing especially in isolated areas of Iran where consanguineous marriages are very common and thus genetic conditions pose a great burden on the society. Genetic counseling and follow-up of such isolated populations has great potential and can drastically improve living conditions. Genetic testing can be offered to such populations and for those who continue to engage in consanguineous marriages can have the option of PND. Diagnosis of Lipoid Proteinosis had been established by dermatologtists previously and patients with their families were referred for genetic counseling. After obtaining written informed consent from families, extensive family history was documented on-site in three separate villages within each others 20-30 km vicinity. Patients were coordinated by the local health service center. DNA was extracted from patient blood samples. PCR reaction was set up for ten exons and nearby intronic regions of the ECM1 gene. PCR products from twelve patients were sequenced and analyzed. All patients harbored the 507delT mutation in exon 6. This mutation generates a new SmaI restriction site at the mutation site. To see if PCR-RFLP can distinguish affected individuals and heterozygotes from healthy homozygotes, thirty-eight individuals were screened by PCR-RFLP. Results documented ten affected individuals (324 bp and 339 bp fragments), nine healthy homozygotes (one 663 bp fragment), and nineteen heterozygotes (663 bp, 324 bp, and 339 bp fragments). Five affected individuals from various age groups underwent MRI and CT scans. Five out of Five demonstrated signal void area in bilateral amygdalae which was confirmed as calcification on CT. Three of the patients with calcification also reported periodic episodes of seizure. Although all our patients harbored the 507delT mutation, all possible clinical presentations were observed; therefore, this unique population negates the possibility of establishing a genotype/phenotype correlation for Lipoid proteinosis in this region of Iran. In conclusion, we can provide genetic testing to affected individuals and propose the possibility of using PCR-RFLP as a cheap and quick screen of the heterozygotes in the population. Genetic counseling,follow-up and education could reduce burden of this disease in Iran.

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