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

Guja Astrea, Antonio Petrucci, Denise Cassandrini, Marco Savarese, Rosanna Trovato, Ludovico Lispi, Anna Rubegni, Manlio Giacanelli, Roberto Massa, Vincenzo Nigro, Filippo M. Santorelli

Research output: Contribution to journalArticle

2 Citations (Scopus)

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. Case presentation: 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.

Original languageEnglish
Article number25
JournalBMC Medical Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - Mar 22 2016

Fingerprint

Distal Myopathies
Muscular Diseases
Mutation
Magnetic Resonance Imaging
Muscles
Myosin Heavy Chains
Genes
Molecular Biology

Keywords

  • Core myopathies
  • Muscle MRI
  • MYH7
  • Next-generation sequencing
  • RYR1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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. / Astrea, Guja; Petrucci, Antonio; Cassandrini, Denise; Savarese, Marco; Trovato, Rosanna; Lispi, Ludovico; Rubegni, Anna; Giacanelli, Manlio; Massa, Roberto; Nigro, Vincenzo; Santorelli, Filippo M.

In: BMC Medical Genetics, Vol. 17, No. 1, 25, 22.03.2016.

Research output: Contribution to journalArticle

Astrea, Guja ; Petrucci, Antonio ; Cassandrini, Denise ; Savarese, Marco ; Trovato, Rosanna ; Lispi, Ludovico ; Rubegni, Anna ; Giacanelli, Manlio ; Massa, Roberto ; Nigro, Vincenzo ; Santorelli, Filippo M. / 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. In: BMC Medical Genetics. 2016 ; Vol. 17, No. 1.
@article{8a71d2b328e041d2a678b8ac9c0ab57d,
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. Case presentation: 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.",
keywords = "Core myopathies, Muscle MRI, MYH7, Next-generation sequencing, RYR1",
author = "Guja Astrea and Antonio Petrucci and Denise Cassandrini and Marco Savarese and Rosanna Trovato and Ludovico Lispi and Anna Rubegni and Manlio Giacanelli and Roberto Massa and Vincenzo Nigro and Santorelli, {Filippo M.}",
year = "2016",
month = "3",
day = "22",
doi = "10.1186/s12881-016-0288-0",
language = "English",
volume = "17",
journal = "BMC Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Myoimaging in the NGS era

T2 - The discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features -a case report

AU - Astrea, Guja

AU - Petrucci, Antonio

AU - Cassandrini, Denise

AU - Savarese, Marco

AU - Trovato, Rosanna

AU - Lispi, Ludovico

AU - Rubegni, Anna

AU - Giacanelli, Manlio

AU - Massa, Roberto

AU - Nigro, Vincenzo

AU - Santorelli, Filippo M.

PY - 2016/3/22

Y1 - 2016/3/22

N2 - 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. Case presentation: 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.

AB - 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. Case presentation: 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.

KW - Core myopathies

KW - Muscle MRI

KW - MYH7

KW - Next-generation sequencing

KW - RYR1

UR - http://www.scopus.com/inward/record.url?scp=85008419328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008419328&partnerID=8YFLogxK

U2 - 10.1186/s12881-016-0288-0

DO - 10.1186/s12881-016-0288-0

M3 - Article

VL - 17

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

M1 - 25

ER -