Manuscrito. -- 2 h.; papel; folio. -- Fondo Universidad de Salamanca; sección Claustros; serie Borradores de claustros. -- Buena conservación. -- Fechas: 16/04/1814 

Vasli N

Harris E

Karamchandani J

Bareke E

Majewski J

Romero NB

Stojkovic T

Barresi R

Tasfaout H

Charlton R

Malfatti E

Bohm J

Marini-Bettolo C

Choquet K

Dicaire MJ

Shao YH

Topf A

O'Ferrall E

Eymard B

Straub V

Blanco G

Lochmuller H

Brais B

Laporte J

Tetreault M

Congenital myopathies define a heterogeneous group of neuromuscular diseases with neonatal or childhood hypotonia and muscle weakness. The genetic cause is still unknown in many patients, precluding genetic counselling and better understanding of the physiopathology. To identify novel genetic causes of congenital myopathies, exome sequencing was performed in three consanguineous families. We identified two homozygous frameshift mutations and a homozygous nonsense mutation in the mitogen-activated protein triple kinase ZAK. In total, six affected patients carry these mutations. Reverse transcription polymerase chain reaction and transcriptome analyses suggested nonsense mRNA decay as a main impact of mutations. The patients demonstrated a generalized slowly progressive muscle weakness accompanied by decreased vital capacities. A combination of proximal contractures with distal joint hyperlaxity is a distinct feature in one family. The low endurance and compound muscle action potential amplitude were strongly ameliorated on treatment with anticholinesterase inhibitor in another patient. Common histopathological features encompassed fibre size variation, predominance of type 1 fibre and centralized nuclei. A peculiar subsarcolemmal accumulation of mitochondria pointing towards the centre of the fibre was a novel histological hallmark in one family. These findings will improve the molecular diagnosis of congenital myopathies and implicate the mitogen-activated protein kinase (MAPK) signalling as a novel pathway altered in these rare myopathies

Newcastle University E-Prints

English

Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion

Universidad de Salamanca (España). Claustro Universitario

Gestion del Repositorio Documental de la Universidad de Salamanca

Borrador de la Junta sobre la impresión de un informe de Instrucción Pública, celebrada el 16 de abril de 1814

Manuscrito. -- 1 h.; papel; folio. -- Fondo Universidad de Salamanca; sección Claustros; serie Borradores de claustros. -- Buena conservación. -- Fechas: 23/04/1814 

Borrador de la Junta sobre la impresión de un informe de Instrucción Pública, celebrada el 23 de abril de 1814

Manuscrito. -- 1 h.; papel; folio. -- Fondo Universidad de Salamanca; sección Claustros; serie Borradores de claustros. -- Buena conservación. -- Fechas: 05/04/1814 

Borrador de la Junta sobre la impresión de un informe de Instrucción Pública, celebrada el 5 de abril de 1814

Manuscrito. -- 1 h.; papel; folio. -- Fondo Universidad de Salamanca; sección Claustros; serie Borradores de claustros. -- Buena conservación. -- Fechas: 13/04/1814 

Borrador de la Junta sobre la impresión de un informe de Instrucción Pública, celebrada el 13 de abril de 1814

Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion

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Newcastle University E-Prints

Gestion del Repositorio Documental de la Universidad de Salamanca

Gestion del Repositorio Documental de la Universidad de Salamanca

Gestion del Repositorio Documental de la Universidad de Salamanca

Gestion del Repositorio Documental de la Universidad de Salamanca