RELN rare variants in myoclonus‐dystonia. Issue 3 (4th February 2015)

• Record Type: Journal Article
• Authors: Groen, Justus L.; Ritz, Katja; Jalalzadeh, Hamid; van der Salm, Sandra M.A.; Jongejan, Aldo; Mook, Olaf R.; Haagmans, Martin A.; Zwinderman, Aeilko H.; Motazacker, Mahdi M.; Hennekam, Raoul C.; Baas, Frank; Tijssen, Marina A.J.
• Is Part Of: Movement disorders. Volume 30:Issue 3(2015)
• Page Start: 415
• Page End: 419
• Publication Date: 2015-02-04
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.26070
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="mds26070-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="mds26070-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="mds26070-sec-0003" sec-type="section"> <title>Results</title> <p>We found co‐segregation of the rare missense variant Thr1904Met in the <italic>RELN</italic> gene. By additional screening of an M‐D cohort, we identified co‐segregation of <italic>RELN</italic> variants in two families (Thr1904Met, Ile1217Met) and identified two sporadic <italic>RELN</italic> mutation carriers (Pro1703Arg, Leu411Ile). Taken together, five of 25 <italic>SGCE</italic>‐negative M‐D patients carried <italic>RELN</italic> rare missense variants.</p> </sec> <sec id="mds26070-sec-0004" sec-type="section"> <title>Conclusion</title> <p>We propose that <italic>RELN</italic> 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</p> </sec> </abstract>