Résumé :
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Communication n° 605 Aim. To account for (i) the variety of periodic paralysis (PP) phenotypes referred for molecular diagnosis, (ii) the positive molecular diagnoses that were made, the frequency of CACNL1A3, SCN4A and KCNJ2 mutations, and their correlation to the referred phenotypes, and (iii) the variety of PP phenotypes lacking a causative mutation. Material and methods. Over five years, samples from 235 independent probands were referred for molecular genetics inquiry after they were diagnosed or suspected with a diagnosis of PP, according to pre-molecular diagnostic data set. In about three quarters of cases, the diagnostic hypothesis of PP was refined as primary hypokalemic [HOPP], primary normo- or hyperkalemic [NK-HKPP], Andersen syndrome [AS], secondary thyrotoxic [TPP]. The rationale of molecular analysis for samples will be presented. Results. (i) The subclassification of the 235 independent PP probands who were referred will be presented. (ii) Causative gene and mutation spectrum, in cases who were positive for molecular inquiry, will be presented, as well as the correlation to the referred phenotypes. (iii) Cases who were negative for the molecular inquiry will be discussed. Conclusion. The genotyping work which was performed during those five years has allowed a positive molecular diagnosis in 43 % of cases referred for diagnosis or suspicion of PP. Further analysis of ion channel genes in well selected negative cases is needed to disclose other PP mutations, which could shed a new light on pathophysiological mechanisms of PP and on skeletal muscle ion channel properties.
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