title: Myoimaging in the NGS era: the discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features--a case report.
abstract: BACKGROUND
  Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family.
  
  
  METHODS
  The proposita, being found to harbor a novel heterozygous mutation in the RYR1 gene (p.Glu294Lys), was initially diagnosed with core myopathy. Subsequently, consideration of muscle magnetic resonance imaging (MRI) features and extension of family study led this diagnosis to be questioned. Use of next-generation sequencing analysis identified a novel mutation in the MYH7gene (p.Ser1435Pro) that segregated in the affected family members.
  
  
  CONCLUSIONS
  This study identified a novel mutation in MYH7 in a family where the conclusive molecular diagnosis was reached through a complicated path. This case report might raise awareness, among clinicians, of the need to interpret NGS data in combination with muscle MRI patterns so as to facilitate the pinpointing of the main molecular etiology in inherited muscle disorders.
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: Guja
authors.initials: G
authors.lastname: Astrea
authors.affiliation: Center for Neuromuscular and Neurological Rare Diseases, S. Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Petrucci
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology (Medical Genetics), Second University of Naples, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Savarese
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Trovato
authors.affiliation: Center for Neuromuscular and Neurological Rare Diseases, S. Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Ludovico
authors.initials: L
authors.lastname: Lispi
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rubegni
authors.affiliation: Center for Neuromuscular and Neurological Rare Diseases, S. Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Giacanelli
authors.affiliation: Department of Systems Medicine (Neurology), University of Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Massa
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology (Medical Genetics), Second University of Naples, Naples, Italy.|Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
authors.affiliation: Molecular Medicine, IRCCS Stella Maris, via dei Giacinti 2, 56128, Calambrone, Pisa, Italy. filippo3364@gmail.com.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D024722:Cardiac Myosins / Q000235:genetics*; D049310:Distal Myopathies / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics
chemical_list: C501641:MYH7 protein, human; D019837:Ryanodine Receptor Calcium Release Channel; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Core myopathies; MYH7; Muscle MRI; Next-generation sequencing; RYR1