RELN rare variants in myoclonus-dystonia.
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RELN rare variants in myoclonus-dystonia.
Groen JL1, Ritz K, Jalalzadeh H, van der Salm SM, Jongejan A, Mook OR, Haagmans MA, Zwinderman AH, Motazacker MM, et al. - February 9, 2015
Mov Disord. 2015 Feb 4. doi: 10.1002/mds.26070.
BACKGROUND: Myoclonus-dystonia (M-D) is a hyperkinetic movement disorder with predominant myoclonic symptoms combined with dystonia of the upper part of the body. A proportion of M-D cases are caused by mutations in the epsilon-sarcoglycan gene. In remaining M-D patients, no genetic factor has been established, indicating genetic heterogeneity.
METHODS:Patients were included in a prospective clinical database and recruited from referral centers and general neurology clinics in The Netherlands. To investigate new genetic causal factors in M-D syndrome, we performed homozygosity mapping combined with exome sequencing in a three-generation M-D family and genetically screened 24 additional patients with M-D.
RESULTS: We found co-segregation of the rare missense variant Thr1904Met in the RELN gene. By additional screening of an M-D cohort, we identified co-segregation of RELN variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic RELN mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 SGCE-negative M-D patients carried RELN rare missense variants.
CONCLUSION:We propose that RELN mutations contribute to the genetic heterogeneity of M-D. Reelin is a large secreted glycoprotein that plays essential roles in the cytoarchitecture of laminated brain structures and modulation of synaptic transmission and plasticity. © 2015 International Parkinson and Movement Disorder Society.
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