TITLE

Clinical features of the DOK7 neuromuscular junction synaptopathy

AUTHOR(S)
Jacqueline Palace; Daniel Lashley; John Newsom-Davis; Judy Cossins; Susan Maxwell; Robin Kennett; Sandeep Jayawant; Yuji Yamanashi; David Beeson
PUB. DATE
June 2007
SOURCE
Brain: A Journal of Neurology;Jun2007, Vol. 130 Issue 6, p1507
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Mutations in DOK7 have recently been shown to underlie a recessive congenital myasthenic syndrome (CMS) associated with small simplified neuromuscular junctions (‘synaptopathy’) but normal acetylcholine receptor and acetylcholinesterase function. We identified DOK7 mutations in 27 patients from 24 kinships. Mutation 1124_1127dupTGCC was common, present in 20 out of 24 kinships. All patients were found to have at least one allele with a frameshift mutation in DOK7 exon 7, suggesting that loss of function(s) associated with the C-terminal region of Dok-7 underlies this disorder. In 15 patients, we were able to study the clinical features in detail. Clinical onset was usually characterized by difficulty in walking developing after normal motor milestones. Proximal muscles were usually more affected than distal, leading to a ‘limb-girdle’ pattern of weakness; although ptosis was often present from an early age, eye movements were rarely involved. Patients did not show long-term benefit from anticholinesterase medication and sometimes worsened, and where tried responded to ephedrine. The phenotype can be distinguished from ‘limb-girdle’ myasthenia associated with tubular aggregates, where DOK7 mutations were not detected and patients respond to anticholinesterase treatments. CMS due to DOK7 mutations are common within our UK cohort and is likely to be under-diagnosed; recognition of the phenotype will help clinical diagnosis, targeted genetic screening and appropriate management.
ACCESSION #
25208678

 

Related Articles

  • The minisequencing method: a simple strategy for genetic screening of MEN 2 families. Bugalho, Maria João; Domingues, Rita; Sobrinho, Luís // BMC Genetics;2002, Vol. 3, p8 

    Background: Multiple endocrine neoplasia type 2 is an autosomal dominant disorder. MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism; MEN 2B by medullary thyroid carcinoma, pheochromocytoma and characteristic stigmata. Activating germline mutations...

  • As Genetic Tests Move Into the Mainstream, Challenges Await for Doctors and Patients. Zielinski, Sarah L. // JNCI: Journal of the National Cancer Institute;3/2/2005, Vol. 97 Issue 5, p334 

    Reports on the challenges faced by physicians in designing guidelines for genetic testing of cancer in the U.S. Association of gene mutations with increased cancer risk; Details on the possibility of a gene susceptibility; Public awareness of familial cancer.

  • Clinical utility gene card for: familial erythrocytosis. Hussein, Kais; Percy, Melanie; McMullin, Mary Frances // European Journal of Human Genetics;May2012, Vol. 20 Issue 5, p1 

    The article offers information on the genetic analysis of familial erythrocytosis, which is an erythropoietin receptor (EPOR) mutation-associated erythrocytosis, familial 1 (ECYT1). It informs that detection of one of the associated gene mutations is required in the diagnosis of ECYT1-4. It...

  • Patients dislike paying for gene testing. McCarty, Mark // Medical Device Daily;6/6/2012, Vol. 16 Issue 107, Special section p1 

    The article focuses on a study from Fox Chase Cancer Center which claims that those who are seen as being at risk for developing one form of cancer or another are reluctant to pay for gene tests. The study reviewed data collected from 406 patients whose family histories suggest cancer-causing...

  • Molecular Testing in Thyroid Cancer. Cappola, Anne R.; Mandel, Susan J. // JAMA: Journal of the American Medical Association;4/10/2013, Vol. 309 Issue 14, p1529 

    The article presents insights on a study of individuals with papillary thyroid cancer (PTC). Particular focus is given to the testing for a mutation in the BRAF gene that has been previously linked with multiple features of aggressive PTC. According to the authors, the analyses indicate that the...

  • Addition of pathology and biomarker information significantly improves the performance of the Manchester scoring system for BRCA1 and BRCA2 testing.  // Journal of Medical Genetics;Dec2009, Vol. 46 Issue 12, p3 

    Background: Selection for genetic testing of BRCA1/BRCA2 is an important area of healthcare. Although testing costs for mutational analysis are falling, costs in North America remain in excess of US$3000 (UK price can be £690). Guidelines in most countries use a 10-20% threshold of detecting...

  • Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky–Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico. Santiago Borrero, Pedro J.; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y.; Izquierdo, Natalio J.; del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A.; Cadilla, Carmen L. // Journal of Investigative Dermatology;Jan2006, Vol. 126 Issue 1, p85 

    Hermansky-Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a...

  • Screening for FXTAS. Jacquemont, Sébastien // European Journal of Human Genetics;Jan2005, Vol. 13 Issue 1, p2 

    Comments on the study "Screening for FMR-1 Premutations in 122 Older Flemish Males Presenting With Ataxia," by H. Van Esch, R. Dorn, D. Bex and colleagues. Availability of magnetic resonance images for the male carriers of the fragile X premutation; Lack of information on the patient population;...

  • A Focused and Efficient Genetic Screening Strategy in the Mouse: Identification of Mutations That Disrupt Cortical Development. Zarbalis, Konstantinos; May, Scott R.; Shen, Yiguo; Ekker, Marc; Rubenstein, John L. R.; Peterson, Andrew S. // PLoS Biology;Aug2004, Vol. 2 Issue 8, p0 

    Although the mechanisms that regulate development of the cerebral cortex have begun to emerge, in large part through the analysis of mutant mice (Boncinelli et al. 2000; Molnar and Hannan 2000; Walsh and Goffinet 2000), many questions remain unanswered. To provide resources for further...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

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

Try another library?
Sign out of this library

Other Topics