title: Late onset of neutral lipid storage disease due to novel PNPLA2 mutations causing total loss of lipase activity in a patient with myopathy and slight cardiac involvement.
abstract: Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report clinical and genetic findings of a patient carrying two novel PNPLA2 mutations (c.696+4A>G and c.553_565delGTCCCCCTTCTCG). She presented at age 39 with right upper limb abduction weakness slowly progressing over the years with asymmetric involvement of proximal upper and lower limb muscles. Cardiological evaluation through ECG and heart echo scan was normal until the age 53, when mild left ventricular diastolic dysfunction was detected. Molecular analysis revealed that only one type of PNPLA2 transcript, with exon 5 skipping, was expressed in patient cells. Such aberrant mRNA causes the production of a shorter ATGL protein, lacking part of the catalytic domain. This is an intriguing case, displaying severe PNPLA2 mutations with clinical presentation characterized by slight cardiac impairment and full expression of severe asymmetric myopathy.
authors.affiliation: Laboratory of Cellular Biochemistry and Molecular Biology, CRIBENS, Catholic University of the Sacred Heart, pz Buonarroti 30, Milan 20145, Italy; Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli, 1, Milan 20123, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Missaglia
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Mora
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gibertini
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Blasevich
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy; Department of Clinical and Community Sciences, University of Milan, Milan, Italy.
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
authors.affiliation: Department of Pharmaceutical Sciences, University of Piemonte Orientale "Amedeo-Avogadro", Novara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Moro
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.affiliation: Servizio di Neuroradiologia, Ospedale San Raffaele, Milan, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Gerevini
authors.affiliation: Laboratory of Cellular Biochemistry and Molecular Biology, CRIBENS, Catholic University of the Sacred Heart, pz Buonarroti 30, Milan 20145, Italy; Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli, 1, Milan 20123, Italy. Electronic address: daniela.tavian@unicatt.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tavian
mesh_terms: D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008049:Lipase / Q000172:deficiency* / Q000235:genetics; D008052:Lipid Metabolism, Inborn Errors / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D009132:Muscles / Q000000981:diagnostic imaging / Q000473:pathology; D009135:Muscular Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D000217:Acyltransferases
chemical_list: D008049:Lipase; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: Cardiomyopathy; Lipid droplets; Lipid metabolism; Neutral lipid storage disease with myopathy; PNPLA2; Triglyceride lipase