Article that correlates Idiopathic dilated cardiomyopathy (DCM) with abnormal protein Nglycosylation.

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  CDGportugal | published 4 months ago | Originally written in English Article that correlates Idiopathic dilated cardiomyopathy (DCM) with abnormal protein Nglycosylation.

  Dear all: Dr Dirk Lefeber from Netherlands and colleagues shared with our community one of their last publicationsand all version is available in this platform in the section learn>documents and the title is:

  Autosomal Recessive Dilated Cardiomyopathy due to DOLK Mutations Results from Abnormal Dystroglycan O-Mannosylation

  Online here: bit.ly/AidpKN

  AUTHOR SUMMARY:
  Idiopathic dilated cardiomyopathy (DCM) is estimated to be of genetic origin in 20%–48% of the patients. Almost all currently known genetic defects show dominant inheritance, although especially in younger children recessive
  causes have been proposed to contribute considerably to DCM. Knowledge of the genetic causes and pathophysiological mechanisms is essential for prognosis and treatment. Here, we studied several individual young
  patients (5–13 years old) with idiopathic and sometimes asymptomatic dilated cardiomyopathy. The key to identification of the gene was the finding of abnormal protein Nglycosylation. Via homozygosity mapping and functional
  knowledge of the N-glycosylation pathway, the causative gene could be identified as dolichol kinase (DOLK). Since DCM is very rare in N-glycosylation disorders (Congenital Disorders of Glycosylation, CDG) and most patients with CDG present with a multisystem involvement, we studied
  the underlying pathophysiological cause of this life threatening
  disease. Biochemical experiments in affected heart tissue showed deficient O-mannosylation of alphadystroglycan, which could be correlated with the dilated cardiomyopathy. Our results thus highlight nonsyndromic DCM as a novel presentation of DOLK-CDG, via deficient Omannosylation of alpha-dystroglycan.