Novel mutation in TCAP manifesting with asymmetric calves and early-onset joint retractions.
A 29-year-old man, born from consanguineous parents, started with toe walking and frequent falls during his second year of life. He developed weakness in lower limbs during the first decade that subsequently extended to upper limbs. On examination, the patient had weakness in proximal muscles of all four limbs and in the tibialis anterior muscle. In addition, he had bilateral Achilles and patellar contractures, bilateral scapular winging, asymmetric calves and a positive Beevor sign, an upward movement of the umbilicus on contraction of rectus femoris due to weakness in the lower part. The muscle biopsy showed dystrophic changes and lobulated fibers. Genetic analysis through a next-generation sequencing panel of genes related to neuromuscular disorders revealed a novel homozygous nonsense mutation (p.Tyr85*) in the TCAP gene. Subsequent western blot assay showed a complete telethonin deficiency. Our observation expands the phenotypic spectrum of TCAP mutations and indicates that telethonin deficiency should be considered in the differential diagnosis of patients presenting with asymmetric calves and early joint retractions.
Servicio de Neurología, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: carlosdefuenmayor@hotmail.com.
Carlos Pablo
CP
de Fuenmayor-Fernández de la Hoz
Unidad de Neuromuscular, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación I+12, Madrid, Spain; Servicio de Neuropatología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Aurelio
A
Hernández-Laín
Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
Montse
M
Olivé
Unidad de Diagnóstico y Tratamiento de Enfermedades Metabólicas Congénitas (UDyTEMC), Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Ana
A
Fernández-Marmiesse
Servicio de Neurología, Hospital Universitario 12 de Octubre, Madrid, Spain; Unidad de Neuromuscular, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación I+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), grupo U-723, Spain.
Cristina
C
Domínguez-González
D000328:Adult; D064211:Connectin / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D003937:Diagnosis, Differential; D006720:Homozygote; D006801:Humans; D007866:Leg / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020125:Mutation, Missense; D010641:Phenotype
D064211:Connectin; C577292:TCAP protein, human
LGMD2G; Muscular dystrophy; TCAP; Telethonin deficiency