A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations

Andrew J M Lewis, Sarah Finlayson, Masliza Mahmod, Theodoros D. Karamitsos, Sairia Dass, Houman Ashrafian, Jane M. Francis, Hugh Watkins, David Beeson, Jacqueline Palace, Stefan Neubauer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Mutations in the GFPT1 and DPAGT1 genes, which encode enzymes associated with roles in protein N-linked glycosylation, have been recently identified in a rare subgroup of patients with congenital myasthenic syndromes (CMSs). Aberrant glycosylation is implicated in the development of cardiomyopathies in the congenital disorders of glycosylation. We investigated whether patients with CMS and GFPT1 or DPAGT1 mutations also had evidence of a cardiac phenotype. Cardiovascular magnetic resonance and echocardiography were used to evaluate cardiac structure and function in patients with GFPT1 (n=2) and DPAGT1 (n=2) mutations. Electrocardiography was abnormal in all, with abnormal repolarization and deep S waves (n=3) or left ventricular hypertrophy by voltage criteria (n=1). Despite normal biventricular size and systolic function, GFPT1/DPAGT1 patients demonstrated late gadolinium enhancement suggestive of myocardial fibrosis (n=4), diastolic dysfunction (n=3) and impaired phosphocreatine to adenosine triphosphate ratio (an indicator of myocardial energetic state), assessed using 31P magnetic resonance spectroscopy (n=2). These findings may reflect incipient cardiomyopathy due to aberrant cardiac glycoprotein function and reinforce the need for cardiac surveillance in patients with disorders due to glycosylation pathway defects.

Original languageEnglish
Pages (from-to)3139-3145
Number of pages7
JournalExperimental and Clinical Cardiology
Volume20
Issue number8
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Phenotype
Congenital Myasthenic Syndromes
Mutation
Glycosylation
Cardiomyopathies
Magnetic Resonance Spectroscopy
Congenital Disorders of Glycosylation
Phosphocreatine
Gadolinium
Left Ventricular Hypertrophy
Echocardiography
Glycoproteins
Electrocardiography
Fibrosis
Adenosine Triphosphate
Enzymes
Genes
Proteins

Keywords

  • Cardiomyopathy
  • Genes
  • Glycoproteins
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Lewis, A. J. M., Finlayson, S., Mahmod, M., Karamitsos, T. D., Dass, S., Ashrafian, H., ... Neubauer, S. (2014). A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations. Experimental and Clinical Cardiology, 20(8), 3139-3145.

A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations. / Lewis, Andrew J M; Finlayson, Sarah; Mahmod, Masliza; Karamitsos, Theodoros D.; Dass, Sairia; Ashrafian, Houman; Francis, Jane M.; Watkins, Hugh; Beeson, David; Palace, Jacqueline; Neubauer, Stefan.

In: Experimental and Clinical Cardiology, Vol. 20, No. 8, 2014, p. 3139-3145.

Research output: Contribution to journalArticle

Lewis, AJM, Finlayson, S, Mahmod, M, Karamitsos, TD, Dass, S, Ashrafian, H, Francis, JM, Watkins, H, Beeson, D, Palace, J & Neubauer, S 2014, 'A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations', Experimental and Clinical Cardiology, vol. 20, no. 8, pp. 3139-3145.
Lewis AJM, Finlayson S, Mahmod M, Karamitsos TD, Dass S, Ashrafian H et al. A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations. Experimental and Clinical Cardiology. 2014;20(8):3139-3145.
Lewis, Andrew J M ; Finlayson, Sarah ; Mahmod, Masliza ; Karamitsos, Theodoros D. ; Dass, Sairia ; Ashrafian, Houman ; Francis, Jane M. ; Watkins, Hugh ; Beeson, David ; Palace, Jacqueline ; Neubauer, Stefan. / A novel cardiac phenotype in patients with GFPT1 or DPAGT1 mutations. In: Experimental and Clinical Cardiology. 2014 ; Vol. 20, No. 8. pp. 3139-3145.
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