Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy

Luca Bello, Paola Melacini, Raffaele Pezzani, Adele D'Amico, Luisa Piva, Emanuela Leonardi, Annalaura Torella, Gianni Soraru, Arianna Palmieri, Gessica Smaniotto, Bruno F. Gavassini, Andrea Vianello, Vincenzo Nigro, Enrico Bertini, Corrado Angelini, Silvio C E Tosatto, Elena Pegoraro

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Protein-o-mannosyl transferase 1 (POMT1) is a glycosyltransferase involved in α-dystroglycan (α-DG) glycosylation. Clinical phenotype in POMT1-mutated patients ranges from congenital muscular dystrophy (CMD) with structural brain abnormalities, to limb-girdle muscular dystrophy (LGMD) with microcephaly and mental retardation, to mild LGMD. No cardiac involvement has until now been reported in POMT1-mutated patients. We report three patients who harbored compound heterozygous POMT1 mutations and showed left ventricular (LV) dilation and/or decrease in myocardial contractile force: two had a LGMD phenotype with a normal or close-to-normal cognitive profile and one had CMD with mental retardation and normal brain MRI. Reduced or absent α-DG immunolabeling in muscle biopsies were identified in all three patients. Bioinformatic tools were used to study the potential effect of POMT1-detected mutations. All the detected POMT1 mutations were predicted in silico to interfere with protein folding and/or glycosyltransferase function. The report on the patients described here has widened the clinical spectrum associated with POMT1 mutations to include cardiomyopathy. The functional impact of known and novel POMT1 mutations was predicted with a bioinformatics approach, and results were compared with previous in vitro studies of protein-o-mannosylase function.

Original languageEnglish
Pages (from-to)1234-1239
Number of pages6
JournalEuropean Journal of Human Genetics
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Limb-Girdle Muscular Dystrophies
Transferases
Cardiomyopathies
Proteins
Mutation
Glycosyltransferases
Muscular Dystrophies
Computational Biology
Intellectual Disability
Dystroglycans
Phenotype
Microcephaly
Protein Folding
Brain
Glycosylation
Computer Simulation
Dilatation
Biopsy

Keywords

  • a-dystroglycan glycosylation
  • cardiomyopathy
  • CMD
  • LGMD
  • POMT1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy. / Bello, Luca; Melacini, Paola; Pezzani, Raffaele; D'Amico, Adele; Piva, Luisa; Leonardi, Emanuela; Torella, Annalaura; Soraru, Gianni; Palmieri, Arianna; Smaniotto, Gessica; Gavassini, Bruno F.; Vianello, Andrea; Nigro, Vincenzo; Bertini, Enrico; Angelini, Corrado; Tosatto, Silvio C E; Pegoraro, Elena.

In: European Journal of Human Genetics, Vol. 20, No. 12, 12.2012, p. 1234-1239.

Research output: Contribution to journalArticle

Bello, L, Melacini, P, Pezzani, R, D'Amico, A, Piva, L, Leonardi, E, Torella, A, Soraru, G, Palmieri, A, Smaniotto, G, Gavassini, BF, Vianello, A, Nigro, V, Bertini, E, Angelini, C, Tosatto, SCE & Pegoraro, E 2012, 'Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy', European Journal of Human Genetics, vol. 20, no. 12, pp. 1234-1239. https://doi.org/10.1038/ejhg.2012.71
Bello, Luca ; Melacini, Paola ; Pezzani, Raffaele ; D'Amico, Adele ; Piva, Luisa ; Leonardi, Emanuela ; Torella, Annalaura ; Soraru, Gianni ; Palmieri, Arianna ; Smaniotto, Gessica ; Gavassini, Bruno F. ; Vianello, Andrea ; Nigro, Vincenzo ; Bertini, Enrico ; Angelini, Corrado ; Tosatto, Silvio C E ; Pegoraro, Elena. / Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy. In: European Journal of Human Genetics. 2012 ; Vol. 20, No. 12. pp. 1234-1239.
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