Genotyping for the FINmaj titin mutation revealed large phenotypic variability, with 9% of 207 heterozygotes exhibiting unusual phenotypes such as proximal leg or posterior lower leg muscle weakness.
Observational (n=386)
The FINmaj titin mutation exhibits large phenotypic variability, suggesting that atypical myopathy/dystrophy phenotypes cannot exclude mutated titin as a cause.
OBJECTIVE: To determine the phenotype variability associated with the specific C-terminal M-line titin mutation known to cause autosomal dominant distal myopathy, tibial muscular dystrophy (TMD; MIM 600334), and limb girdle muscular dystrophy 2J (LGMD2J). METHODS: Three hundred eighty-six individuals were genotyped for the Finnish founder mutation in titin (FINmaj) causing TMD/LGMD2J. RESULTS: Two hundred seven patients were heterozygous for the mutation. Among these patients, 189 (91%) had a more common phenotype compatible with the classic description of TMD. However, 18 (9%) had unusual phenotypes such as proximal leg or posterior lower leg muscle weakness and atrophy even at onset. Four patients were confirmed homozygotes representing the LGMD2J phenotype. These homozygotes were half of the eight LGMD patients previously described in the original large consanguineous kindred. CONCLUSIONS: Large variability of phenotypic expression caused by just one mutation, the Finnish FINmaj, suggests that no certain phenotype of myopathy/dystrophy can be excluded from being caused by mutated titin. Yet unknown homozygous or compound heterozygous titin mutations without phenotype in the heterozygote carriers may be responsible for undetermined recessive MD and LGMD.
Udd et al. (Tue,) conducted a observational in Titinopathies (tibial muscular dystrophy and limb girdle muscular dystrophy 2J) (n=386). Genotyping for FINmaj mutation was evaluated on Phenotype variability associated with the FINmaj titin mutation. Genotyping for the FINmaj titin mutation revealed large phenotypic variability, with 9% of 207 heterozygotes exhibiting unusual phenotypes such as proximal leg or posterior lower leg muscle weakness.