TY - JOUR

T1 - Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy

AU - Citirak, Gülsenay

AU - Witting, Nanna

AU - Duno, Morten

AU - Werlauff, Ulla

AU - Petri, Helle

AU - Vissing, John

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2014/4

Y1 - 2014/4

N2 - Congenital myopathies are difficult to classify correctly through molecular testing due to the size and heterogeneity of the genes involved. Therefore, the prevalence of the various genetic causes of congenital myopathies is largely unknown. In our cohort of 94 patients with congenital myopathy, two related female patients and two sporadic, male patients were found to carry mutations in the tropomyosin 2 (TPM2) and tropomyosin 3 (TPM3) genes, respectively. This indicates a low (4.3%) frequency of TPM2 and TPM3 mutations as a cause of congenital myopathy. Compared to previously described patients carrying the same mutations as found in our study (c.503G>A, and c.502C>T in TPM3, and c.415_417delGAG in TPM2), clinical presentation and muscle morphological findings differed in our patients. Differences included variation in distribution of muscle weakness, presence of scoliosis and ptosis, physical performance and joint contractures. The variation in clinical profiles emphasizes the phenotypic heterogeneity. However, common features were also present, such as onset of symptoms in infancy or childhood, musculoskeletal deformities and normal or low plasma levels of creatine kinase. One patient had nemaline myopathy and fiber size disproportion, while three patients had congenital fiber type disproportion (CFTD) on muscle biopsies. TPM2-related CFTD has only been described in two cases, indicating that mutations in TPM2 are rare causes of CFTD.

AB - Congenital myopathies are difficult to classify correctly through molecular testing due to the size and heterogeneity of the genes involved. Therefore, the prevalence of the various genetic causes of congenital myopathies is largely unknown. In our cohort of 94 patients with congenital myopathy, two related female patients and two sporadic, male patients were found to carry mutations in the tropomyosin 2 (TPM2) and tropomyosin 3 (TPM3) genes, respectively. This indicates a low (4.3%) frequency of TPM2 and TPM3 mutations as a cause of congenital myopathy. Compared to previously described patients carrying the same mutations as found in our study (c.503G>A, and c.502C>T in TPM3, and c.415_417delGAG in TPM2), clinical presentation and muscle morphological findings differed in our patients. Differences included variation in distribution of muscle weakness, presence of scoliosis and ptosis, physical performance and joint contractures. The variation in clinical profiles emphasizes the phenotypic heterogeneity. However, common features were also present, such as onset of symptoms in infancy or childhood, musculoskeletal deformities and normal or low plasma levels of creatine kinase. One patient had nemaline myopathy and fiber size disproportion, while three patients had congenital fiber type disproportion (CFTD) on muscle biopsies. TPM2-related CFTD has only been described in two cases, indicating that mutations in TPM2 are rare causes of CFTD.

KW - Adult

KW - Cohort Studies

KW - DNA Mutational Analysis

KW - Female

KW - Humans

KW - Male

KW - Muscle, Skeletal

KW - Mutation

KW - Myotonia Congenita

KW - Phenotype

KW - Tropomyosin

KW - Young Adult

U2 - 10.1016/j.nmd.2013.12.008

DO - 10.1016/j.nmd.2013.12.008

M3 - Journal article

C2 - 24507666

VL - 24

SP - 325

EP - 330

JO - Journal of Neuromuscular Diseases

JF - Journal of Neuromuscular Diseases

SN - 0960-8966

IS - 4

ER -