title: 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).
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.
authors: NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, MD, USA. tyler.pierson@cshs.org
authors: Tyler Mark
authors: TM
authors: Pierson
authors: Thomas
authors: T
authors: Markello
authors: John
authors: J
authors: Accardi
authors: Lynne
authors: L
authors: Wolfe
authors: David
authors: D
authors: Adams
authors: Murat
authors: M
authors: Sincan
authors: Noor M
authors: NM
authors: Tarazi
authors: Karin Fuentes
authors: KF
authors: Fajardo
authors: Praveen F
authors: PF
authors: Cherukuri
authors: Ilda
authors: I
authors: Bajraktari
authors: Katy G
authors: KG
authors: Meilleur
authors: Sandra
authors: S
authors: Donkervoort
authors: Mina
authors: M
authors: Jain
authors: Ying
authors: Y
authors: Hu
authors: Tanya J
authors: TJ
authors: Lehky
authors: Pedro
authors: P
authors: Cruz
authors: James C
authors: JC
authors: Mullikin
authors: Carsten
authors: C
authors: Bonnemann
authors: William A
authors: WA
authors: Gahl
authors: Cornelius F
authors: CF
authors: Boerkoel
authors: Cynthia J
authors: CJ
authors: Tifft
mesh_terms: D002648:Child; D002874:Chromosome Mapping; D003680:Deglutition Disorders / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012120:Respiration Disorders / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C522055:MEGF10, human; D008565:Membrane Proteins