title: Telethonin-deficiency initially presenting as a congenital muscular dystrophy.
abstract: Congenital muscular dystrophies are defined by congenital or infantile onset of muscle weakness; while 12 culprit genes have been identified, many cases remain molecularly uncharacterized. On the other hand, mutations in the telethonin gene (TCAP) have been associated with a rare form of recessive limb girdle muscular dystrophy, usually presenting in the second decade. So far, three different mutations in telethonin have been reported in patients suffering from limb muscular dystrophy type 2G. We have identified a novel telethonin mutation in a child presenting with mildly delayed motor development and muscle weakness from infancy, clinically improving over the first decade, indicative of a CMD. Muscle biopsy showed a dystrophic process, with preserved laminin α2, collagen VI, and α-dystroglycan, but absent telethonin immunolabeling. Sequence analysis of TCAP showed a novel non-sense p.Gln58X (c.172C>T) homozygous mutation. Our observation indicates that telethonin deficiency may present in infancy with clinical features overlapping with mild forms of α-dystroglycanopathy. Therefore telethonin analysis should be performed in patients suffering from congenital muscular dystrophy of unknown cause.
authors.affiliation: AP-HP, Centre de Référence des Maladies Neuromusculaires Paris-Est, Groupe Hospitalier-Universitaire Pitié-Salpêtrière, Paris F-75013, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Ferreiro
authors.forename: Monica
authors.initials: M
authors.lastname: Mezmezian
authors.forename: Montse
authors.initials: M
authors.lastname: Olivé
authors.forename: Danielle
authors.initials: D
authors.lastname: Herlicoviez
authors.forename: Michel
authors.initials: M
authors.lastname: Fardeau
authors.forename: Pascale
authors.initials: P
authors.lastname: Richard
authors.forename: Norma Beatriz
authors.initials: NB
authors.lastname: Romero
mesh_terms: D001706:Biopsy; D002648:Child; D024142:Collagen Type VI / Q000378:metabolism; D064211:Connectin; D049030:Dystroglycans / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000209:etiology* / Q000235:genetics; D049288:Muscular Dystrophies, Limb-Girdle / Q000209:etiology* / Q000235:genetics / Q000473:pathology
chemical_list: D024142:Collagen Type VI; D064211:Connectin; D007797:Laminin; D009124:Muscle Proteins; C577292:TCAP protein, human; C102645:laminin alpha 2; D049030:Dystroglycans