This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citing articles on HighWire  • Citing articles on Web of Science (8)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurogenetics  • Neuromuscular diseases  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Genetic and Clinical Analysis

Peter Hedera, MD; Elizabeth M. Petty, MD; Melanie R. Bui, BS; Mila Blaivas, MD; John K. Fink, MD

Arch Neurol. 2003;60:1321-1325.

Background  Distal myopathies (MPDs) are genetically heterogeneous. Genetic causes within this subgroup of muscle disorders remain largely unknown. An MPD linked to chromosome 14q11-q13 (MPD1) is rare, and to our knowledge, only one family with definitive linkage has been described.

Objective  To describe the results of clinical and genetic analysis of the second kindred with MPD1.

Patients and Methods  We have identified a family with an MPD segregating in an autosomal dominant fashion. We tested linkage to previously identified genetic loci on chromosomes 2p, 2q, and 14q. The coding sequence of PABP2 (the polyadenylate-binding protein 2 gene) was analyzed.

Results  Every affected individual had selective weakness of foot extensors, with the average age of symptom onset at 20 years. Some patients also had proximal weakness, but none had signs of finger or hand extensor muscle involvement, even in advanced stages of the disease. Two typically affected individuals had signs of idiopathic dilated cardiomyopathy. Genetic analysis detected a tight linkage to chromosome 14q11-q13. Recombination at the telomeric end of the 14q11-q13 locus was found in an unaffected individual who was not considered to be at risk, potentially reducing the locus interval by 2 centimorgans. No mutations in the PABP2 gene were identified.

Conclusions  To our knowledge, our described family is only the second known kindred with a chromosome 14–linked MPD in whom the linkage has been unequivocally established. We did not detect signs of involvement of hand or finger extensors and neck muscles, seen in the original family with MPD1. The degree and frequency of proximal weakness seem to be more prominent than in other patients with MPD1. Haplotype analysis suggests that the gene is located between polymorphic microsatellite markers D14S283 and D14S1034 on chromosome 14q11-q13. The presence of cardiomyopathy in some affected individuals may help in the identification of candidate genes.

From the Department of Neurology, University of Michigan Medical Center (Drs Hedera and Fink and Ms Bui); the Division of Molecular Medicine and Genetics, Departments of Internal Medicine (Dr Petty), Human Genetics (Dr Petty), and Pathology (Dr Blaivas), University of Michigan; and the Geriatric Research Education and Clinical Center, Ann Arbor Veterans Affairs Medical Center (Dr Fink), Ann Arbor. Dr Hedera is now with the Department of Neurology, Vanderbilt University, Nashville, Tenn.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy
Lamont et al.
J. Neurol. Neurosurg. Psychiatry 2006;77:208-215.
ABSTRACT | FULL TEXT