title: Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy.
abstract: While TPM2 mutations identified so far in muscular diseases were all associated with a dominant inheritance pattern, we report the identification of a homozygous null allele mutation in the TPM2 gene in a patient who presented with a recessive form of nemaline myopathy associated with a non-lethal multiple pterygium syndrome (Escobar-MPS MIM# 265000). The TPM2 mutation led to a complete absence of the skeletal muscle isoform of beta-tropomyosin not compensated by expression of other beta-tropomyosin isoforms. Escobar syndrome has been recently described as a prenatal form of myasthenia associated with recessive mutations in genes of the neuromuscular junction (CHRNG, CHRNA1, CHRND, RAPSN). This observation expands the cause of Escobar variant-MPS to a component of the contractile apparatus. This first report of the clinical expression of the complete absence of TPM2 in human indicated that TPM2 expression at the early period of prenatal life plays a major role for normal fetal movements.
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire & Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Monnier
authors.forename: Joel
authors.initials: J
authors.lastname: Lunardi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Marty
authors.forename: Paulette
authors.initials: P
authors.lastname: Mezin
authors.forename: Annick
authors.initials: A
authors.lastname: Labarre-Vila
authors.forename: Klaus
authors.initials: K
authors.lastname: Dieterich
authors.forename: Pierre Simon
authors.initials: PS
authors.lastname: Jouk
mesh_terms: D000328:Adult; D000462:Algeria / Q000208:ethnology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000002:abnormalities / Q000378:metabolism* / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D014335:Tropomyosin