Facing the genetic heterogeneity in neuromuscular disorders: linkage analysis as an economic diagnostic approach towards the molecular diagnosis
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
The identification of an ever increasing number of gene defects in patients with neuromuscular disorders has disclosed both marked phenotype and genotype variability and considerable disease overlap. In order to offer an economic strategy to characterise the molecular defect in patients with unclassified neuromuscular disorders, we designed DNA marker sets for linkage analysis of 62 distinct neuromuscular disorders gene loci, including all known muscular dystrophies, congenital myopathies, congenital myasthenic syndromes and myotonias. Genotyping of marker loci of 140 clinically well-characterised families with unclassified neuromuscular disorders reduced the number of candidates to one or two genes in 49 % of the families. Subsequent mutation analysis and genome-wide scans enabled the determination of the genetic defect in 31 % of the families including the identification of a new gene and a new mutation in an unexpected candidate gene. This highlights the effective application of this approach both for diagnostic strategies as well as for the identification of new loci and genes.
Details
Original language | English |
---|---|
Pages (from-to) | 4-13 |
Number of pages | 10 |
Journal | Neuromuscular Disorders |
Volume | 16 |
Issue number | 1 |
Publication status | Published - Jan 2006 |
Peer-reviewed | Yes |
External IDs
researchoutputwizard | legacy.publication#13686 |
---|---|
Scopus | 30644464184 |
PubMed | 16378727 |
researchoutputwizard | legacy.publication#8451 |
researchoutputwizard | legacy.publication#13771 |
Keywords
Keywords
- DNA Mutational Analysis/methods, Databases, Genetic/statistics & numerical data, Diagnosis, Differential, Family Health, Genetic Heterogeneity, Genotype, Humans, Molecular Diagnostic Techniques/economics, Muscle Proteins/genetics, Neuromuscular Diseases/classification