Udd B, Vihola A, Sarparanta J, Richard I, Hackman P
Neurological Department, Vaasa Central Hospital, Finland.
Neurology. 2005 Feb 22;64(4):636-42. doi: 10.1212/01.WNL.0000151853.50144.82.
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).
Three hundred eighty-six individuals were genotyped for the Finnish founder mutation in titin (FINmaj) causing TMD/LGMD2J.
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.
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.
确定与已知可导致常染色体显性遗传性远端肌病、胫骨型肌营养不良（TMD；MIM 600334）和肢带型肌营养不良2J型（LGMD2J）的特定C末端肌联蛋白突变相关的表型变异性。
对386名个体进行基因分型，检测导致TMD/LGMD2J的芬兰肌联蛋白始祖突变（FINmaj）。
207名患者为该突变的杂合子。在这些患者中，189名（91%）具有与TMD经典描述相符的更常见表型。然而，18名（9%）具有不寻常的表型，如发病时即出现近端腿部或小腿后部肌肉无力和萎缩。4名患者被确认为纯合子，表现为LGMD2J表型。这些纯合子占原始大型近亲家系中先前描述的8名LGMD患者的一半。
仅一种突变，即芬兰FINmaj，所导致的表型表达存在很大变异性，这表明任何肌病/肌营养不良的特定表型都不能排除由突变的肌联蛋白引起。然而，在杂合子携带者中无表型的未知纯合或复合杂合肌联蛋白突变可能是未确定的隐性肌营养不良和LGMD的病因。
