TITLE

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

AUTHOR(S)
Vasli, Nasim; Harris, Elizabeth; Karamchandani, Jason; Bareke, Eric; Majewski, Jacek; Romero, Norma B.; Stojkovic, Tanya; Barresi, Rita; Tasfaout, Hichem; Charlton, Richard; Malfatti, Edoardo; Bohm, Johann; Marini-Bettolo, Chiara; Choquet, Karine; Dicaire, Marie-Joseé; Yi-Hong Shao; Topf, Ana; O'Ferrall, Erin; Eymard, Bruno; Straub, Volker
PUB. DATE
January 2017
SOURCE
Brain: A Journal of Neurology;Jan2017, Vol. 140 Issue 1, p37
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
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.
ACCESSION #
120486161

 

Related Articles

  • A mosaic maternal splice donor mutation in the EHMT1 gene leads to aberrant transcripts and to Kleefstra syndrome in the offspring. Rump, Andreas; Hildebrand, Laura; Tzschach, Andreas; Ullmann, Reinhard; Schrock, Evelin; Mitter, Diana // European Journal of Human Genetics;Aug2013, Vol. 21 Issue 8, p887 

    The euchromatic histone-lysine N-methyltransferase 1 (EHMT1) gene was examined in a 3-year-old boy with characteristic clinical features of Kleefstra syndrome. Sequencing of all 27 EHMT1 exons revealed a novel mutation, NM_024757.4:c.2712+1G>A, which affects the splice donor of intron 18....

  • Nemaline rod myopathy: A rare form of myopathy. Sharma, M. C.; Gulati, S.; Atri, S.; Seth, R.; Kalra, V.; Das, T. K.; Sarkar, C. // Neurology India;Jan-Mar2007, Vol. 55 Issue 1, p70 

    Nemaline rod myopathy (NM) is a rare form of congenital myopathy characterized by slowly progressive or nonprogressive muscle weakness and pathognomonic rod-like structures within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of...

  • Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. Pfeffer, Gerald; Griffin, Helen; Pyle, Angela; Horvath, Rita; Chinnery, Patrick F. // Brain: A Journal of Neurology;Apr2014, Vol. 137 Issue 4, pe271 

    No abstract available.

  • WNK4 kinase regulates surface expression of the human sodium chloride cotransporter in mammalian cells. Cai, H.; Cebotaru, V.; Wang, Y.-H.; Zhang, X.-M.; Cebotaru, L.; Guggino, S. E.; Guggino, W. B. // Kidney International;Jun2006, Vol. 69 Issue 12, p2162 

    Pseudohypoaldosteronism type II (PHA II) is caused by mutations of two members of WNK ((with no lysine (k)) kinase family. WNK4 wild type (WT) has been shown to inhibit the activity and surface expression of sodium chloride cotransporter (NCC) when expressed in Xenopus oocytes. Here, we have...

  • Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex. Kirschner, Lawrence S.; Carney, J. Aidan; Pack, Svetlana D.; Taymans, Susan E.; Giatzakis, Christoforos; Cho, Yee Sook; Cho-Chung, Yoon S.; Stratakis, Constantine A. // Nature Genetics;Sep2000, Vol. 26 Issue 1, p89 

    Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22?24...

  • Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Goldfarb, Lev G.; Park, Kye-Yoon; Cervenáková, Larisa; Gorokhova, Svetlana; Lee, Hee-Suk; Vasconcelos, Olavo; Nagle, James W.; Semino-Mora, Christina; Sivakumar, Kumaraswamy; Dalakas, Marinos C. // Nature Genetics;Aug98, Vol. 19 Issue 4, p402 

    Desmin-related myopathy (OMIM 601419) is a familial disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. The...

  • A novel missense mutation in the GNE gene in an Iranian patient with hereditary inclusion body myopathy. Behnam, Mahdiyeh; Shin Jin-Hong; Dae-Seong Kim; Basiri, Keivan; Nilipour, Yalda; Sedghi, Maryam // Journal of Research in Medical Sciences;Aug2014, Vol. 19 Issue 8, p792 

    Hereditary inclusion body myopathy (hIBM) is an adult-onset hereditary myopathy, usually with distal onset and quadriceps sparing. This myopathy is autosomal recessive and associated to UPD-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations. In this study, we...

  • Clinical utility gene card for: Laing distal myopathy. Lamont, Phillipa; Wallefeld, William; Davis, Mark; Udd, Bjarne; Laing, Nigel // European Journal of Human Genetics;Mar2011, Vol. 19 Issue 3, p1 

    The article offers information on the clinical utility gene card describing the characteristics and genetic aspects of Laing distal myopathy.

  • Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening. Nigel Laing // Journal of Muscle Research & Cell Motility;Dec2008, Vol. 29 Issue 6-8, p247 

    Abstract  Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological...

Share

Read the Article

Courtesy of

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics