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Presence of Alanine-to-Valine Substitutions in Myofibrillogenesis Regulator 1 in Paroxysmal Nonkinesigenic Dyskinesia
Confirmation in 2 Kindreds
Dong-Hui Chen, MD, PhD;
Mark Matsushita, BS;
Shirley Rainier, PhD;
Brandon Meaney, MD;
Lisa Tisch, BS;
Abreham Feleke, BS;
John Wolff, BS;
Hillary Lipe, ARNP;
John Fink, MD;
Thomas D. Bird, MD;
Wendy H. Raskind, MD, PhD
Arch Neurol. 2005;62:597-600.
Background Paroxysmal nonkinesigenic dyskinesia (PNKD) is a rare disorder characterized by attacks of involuntary movements brought on by stress, alcohol, or caffeine, but not by movement. An autosomal dominant form of this disorder was mapped to chromosome 2q33-36, and different missense mutations in exon 1 of the myofibrillogenesis regulator 1 (MR1) gene were identified recently in 2 kindreds.
Objectives To describe studies on a new pedigree with PNKD, to explore the possibility of locus heterogeneity, and to further delineate the spectrum of mutations in MR1 in 2 families with PNKD.
Design, Setting, and Patients All 10 exons of MR1 were sequenced in DNA from members of 2 pedigrees with autosomal dominant PNKD.
Results Different missense mutations in exon 1 of MR1 that cosegregate with disease were identified in each multiplex family. These single-nucleotide mutations predicted substitution of valine for alanine in residue 7 in one family and residue 9 in the other. The same mutations were found in the only 2 families previously published. Family history and haplotype analysis make it unlikely that the families with the same mutations are related.
Conclusions The function of MR1 is unknown, but the 2 mutations identified in the 4 families with PNKD studied to date are predicted to disrupt the amino terminal  -helix suggesting that this region of the gene is critical for proper gene function under stressful conditions. Study of additional families will be important to determine whether analysis of a single exon (MR1 exon 1) is sufficient for genetic testing purposes.
Author Affiliations: Departments of Neurology (Drs Chen and Bird and Ms Lipe), Medicine (Messrs Matsushita, Feleke, and Wolff; Ms Tisch; and Dr Raskind), and Psychiatry (Dr Raskind), University of Washington, and the Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center (Dr Bird), Seattle, Wash; Pediatric Neurology, Department of Neurology, University of Michigan (Drs Rainier and Fink), and the Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center (Dr Fink), Ann Arbor, Mich; and Department of Pediatrics, McMaster University, Hamilton, Ontario (Dr Meaney).
RELATED LETTER
Significance of Recurrent Mutations in the Myofibrillogenesis Regulator 1 Gene
Ana Djarmati, Marina Svetel, Dragana Momcilovic, Vladimir Kostic, and Christine Klein
Arch Neurol. 2005;62(10):1641.
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