biostudies-literatureMencacci NEUniversity College London HospitalsNHLBI NIH HHSMedical Research CouncilBiomedical Research CentersUniversity College LondonNational Institute for Health Research (NIHR)Wellcome Trust5326-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4550822biostudies-literatureUnknown24(18)Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ∼30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome AggregatiHuman molecular geneticsThe CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort.PMC4550822RC2 HL102926NF-SI-0507-10376RC2 HL102925UC2 HL102923RC2 HL102924RC2 HL102923WT089698/Z/09/ZUC2 HL102924MC_G1000735UC2 HL102925UC2 HL102926RC2 HL103010NF-SI-0513-10064089698UC2 HL103010Nardocci NPittman AMHardy JCarecchio MZorzi GGasser TBandres-Ciga SMencacci NEWood NWGaravaglia BR'bibo LKlein CBhatia KPWeissbach ALohmann EBatla AfalseThe CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort.Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ∼30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregati2015-01-01T00:00:00Z2015 Sep2026-05-30T11:18:04.653Z2019-03-27T01:57:23ZS-EPMC45508222615702410.1093/hmg/ddv255