Novel SNP array analysis and exome sequencing detect a homozygous exon 7 deletion of MEGF10 causing early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD)

Tyler Mark Pierson, Thomas Markello, John Accardi, Lynne Wolfe, David Adams, Murat Sincan, Noor M. Tarazi, Karin Fuentes Fajardo, Praveen F. Cherukuri, Ilda Bajraktari, Katy G. Meilleur, Sandra Donkervoort, Mina Jain, Ying Hu, Tanya J. Lehky, Pedro Cruz, James C. Mullikin, Carsten Bonnemann, William A. Gahl, Cornelius F. BoerkoelCynthia J. Tifft

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) is a myopathic disorder associated with mutations in MEGF10. By novel analysis of SNP array hybridization and exome sequence coverage, we diagnosed a 10-years old girl with EMARDD following identification of a novel homozygous deletion of exon 7 in MEGF10. In contrast to previously reported EMARDD patients, her weakness was more prominent proximally than distally, and involved her legs more than her arms. MRI of her pelvis and thighs showed muscle atrophy and fatty replacement. Ultrasound of several muscle groups revealed dense homogenous increases in echogenicity. Cloning and sequencing of the deletion breakpoint identified features suggesting the mutation arose by fork stalling and template switching. These findings constitute the first genomic deletion causing EMARDD, expand the clinical phenotype, and provide new insight into the pattern and histology of its muscular pathology.

Original languageEnglish (US)
Pages (from-to)483-488
Number of pages6
JournalNeuromuscular Disorders
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

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Keywords

  • Deletion analysis
  • EMARDD
  • Exome sequencing
  • MEGF10
  • Myopathy
  • SNP array

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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