In:
Movement Disorders, Wiley, Vol. 30, No. 3 ( 2015-03), p. 415-419
Abstract:
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
Type of Medium:
Online Resource
ISSN:
0885-3185
,
1531-8257
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2041249-6