Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy

M. C. Speer, J. M. Gilchrist, J. M. Stajich, P. C. Gaskell, G. A. Westbrook, S. K. Horrigan, L. Bartoloni, L. H. Yamaoka, W. K. Scott, M. A. Pericak-Vance

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Anticipation, an increase in severity or decrease in age of onset (AO) inherent in the transmission of the disease gene from affected parent to affected child, has been increasingly described in human disease. To assess anticipation in a large kindred in which autosomal dominant limb-girdle muscular dystrophy (LGMD1A) is segregating, age of disease onset was collected from patient interviews of affected family members. A total of 25 parent-offspring pairs, in which the parents are three (3R), four (4R), or five (5R) generations removed from a common founding ancestor, were available for analysis. Life table analyses showed significant decreases in age at first reported symptoms in the offspring of the 3R (χ2 = 5.55, p = 0.02) and 4R (χ2 = 7.81, p = 0.005) parents. Pairwise analyses confirmed this decrease with a median decrease of 13 years in transmission to offspring from 3R parents and 18 years in transmission to offspring from 4R parents. The finding of anticipation in this pedigree suggests that the mutation in LGMD1A may be the result of the expansion of an unstable trinucleotide repeat.

Original languageEnglish (US)
Pages (from-to)305-308
Number of pages4
JournalJournal of medical genetics
Volume35
Issue number4
DOIs
StatePublished - 1998

Keywords

  • Anticipation
  • Autosomal dominant
  • Limb-girdle
  • Muscular dystrophy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy'. Together they form a unique fingerprint.

  • Cite this

    Speer, M. C., Gilchrist, J. M., Stajich, J. M., Gaskell, P. C., Westbrook, G. A., Horrigan, S. K., Bartoloni, L., Yamaoka, L. H., Scott, W. K., & Pericak-Vance, M. A. (1998). Evidence for anticipation in autosomal dominant limb-girdle muscular dystrophy. Journal of medical genetics, 35(4), 305-308. https://doi.org/10.1136/jmg.35.4.305