Abstract |
Mutations in C-terminal titin cause autosomal dominant tibial muscular dystrophy (TMD) as reported previously. Samples from 25 new families and 25 sporadic new distal myopathy cases were screened for titin mutations. Three novel mutations were discovered in two families from Spain and two families from France. Two mutations, g.292998delT and g.293376delA lead to frameshift and premature stop codons in the second last and the last titin gene (TTN) exons, Mex5 and Mex6, respectively. The third was a nonsense mutation g.293379C>T (p.Q33396X) in Mex6. Patients with the upstream Mex5 mutation showed a more severe phenotype with earlier onset implying a genotype-phenotype correlation.
|
Authors | Peter Hackman, Sylvie Marchand, Jaakko Sarparanta, Anna Vihola, Isabelle Pénisson-Besnier, Bruno Eymard, Jose Manuel Pardal-Fernández, El-Hadi Hammouda, Isabelle Richard, Isabel Illa, Bjarne Udd |
Journal | Neuromuscular disorders : NMD
(Neuromuscul Disord)
Vol. 18
Issue 12
Pg. 922-8
(Dec 2008)
ISSN: 0960-8966 [Print] England |
PMID | 18948003
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Codon, Nonsense
- Connectin
- Muscle Proteins
- TTN protein, human
- Protein Kinases
|
Topics |
- Adult
- Aged
- Base Sequence
- Blotting, Western
- Codon, Nonsense
- Connectin
- DNA Mutational Analysis
- Distal Myopathies
(genetics, metabolism, pathology)
- Female
- Frameshift Mutation
- Genetic Predisposition to Disease
- Genotype
- Humans
- Male
- Middle Aged
- Molecular Sequence Data
- Muscle Proteins
(genetics, metabolism)
- Muscle, Skeletal
(metabolism, pathology)
- Mutation
- Pedigree
- Phenotype
- Protein Kinases
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Severity of Illness Index
- Tomography Scanners, X-Ray Computed
|