title: The first Italian family with tibial muscular dystrophy caused by a novel titin mutation.
abstract: Tibial muscular dystrophy (TMD) or Udd myopathy is an autosomal dominant distal myopathy with late onset, at first described in the Finnish population. We report here the first Italian cases of TTN mutated titinopathy. The proband, a 60 year-old female, had the first muscular signs at the age of 59 years, with difficulty in walking and right foot drop. Muscle imaging showed selective fatty degenerative change in the anterior compartment of leg muscles. Her 67 year-old brother, started to show muscle weakness, pain at lower limbs and hypertrophy of calf muscles at the age of 66 years. Their mother began to show foot drop and impaired walking from the age of 60 years. Other relatives are reported to be affected in a similar way. Because the phenotype appeared compatible with TMD, we analyzed the TTN gene in the DNA of the proband and we identified a heterozygous mutation 293326A>C. This mutation is also present in the brother and in the other affected individuals of the same family. The mutation predicts a His33378Pro change located next to the previously known Belgian TMD mutation. The mutation was not found in 100 Italian control DNA samples. Then, since the introduction of a proline in the last domain of titin was previously known to cause TMD in French families, we can conclude that this missense mutation is the obvious pathogenetic mutation in the affected patients. No other disease causing mutations in the TTN gene have so far been reported in the Italian population.
authors.affiliation: Medical Genetics, Department Molecular Biology, University of Siena, Policlinico Le Scotte, viale Bracci 2, 53100, Siena, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pollazzon
authors.forename: Tiina
authors.initials: T
authors.lastname: Suominen
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Carluccio
authors.forename: Mauro
authors.initials: M
authors.lastname: Mondelli
authors.forename: Annabella
authors.initials: A
authors.lastname: Marozza
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Peter
authors.initials: P
authors.lastname: Hackman
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000368:Aged; D064211:Connectin; D004252:DNA Mutational Analysis; D049310:Distal Myopathies / Q000000981:diagnostic imaging / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D006639:Histidine; D011392:Proline; D011494:Protein Kinases