OBJECTIVE: To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. PATIENTS AND METHODS: Twenty-five CMS patients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSN p.N88K was performed in all patients. RESULTS: We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNE c.70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNE c.70insG derives from a common ancestor. CONCLUSIONS: Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000.
OBJECTIVE: To perform genetic testing of patients with congenital myasthenic syndromes (CMS) from the Southern Brazilian state of Parana. PATIENTS AND METHODS: Twenty-five CMSpatients from 18 independent families were included in the study. Known CMS genes were sequenced and restriction digest for the mutation RAPSNp.N88K was performed in all patients. RESULTS: We identified recessive mutations of CHRNE in ten families, mutations in DOK7 in three families and mutations in COLQ, CHRNA1 and CHRNB1 in one family each. The mutation CHRNEc.70insG was found in six families. We have repeatedly identified this mutation in patients from Spain and Portugal and haplotype studies indicate that CHRNEc.70insG derives from a common ancestor. CONCLUSIONS: Recessive mutations in CHRNE are the major cause of CMS in Southern Brazil with a common mutation introduced by Hispanic settlers. The second most common cause is mutations in DOK7. The minimum prevalence of CMS in Parana is 0.18/100 000.
Authors: Eduardo de Paula Estephan; Cláudia Ferreira da Rosa Sobreira; André Clériston José Dos Santos; Pedro José Tomaselli; Wilson Marques; Roberta Paiva Magalhães Ortega; Marcela Câmara Machado Costa; André Macedo Serafim da Silva; Rodrigo Holanda Mendonça; Vitor Marques Caldas; Antonio Alberto Zambon; Osório Abath Neto; Paulo Eurípedes Marchiori; Carlos Otto Heise; Umbertina Conti Reed; Yoshiteru Azuma; Ana Töpf; Hanns Lochmüller; Edmar Zanoteli Journal: J Neurol Date: 2018-01-30 Impact factor: 4.849