Identification of an intragenic deletion in the SGCB gene through a re-evaluation of negative next generation sequencing results

Teresa Giugliano, Marina Fanin, Marco Savarese, Giulio Piluso, Corrado Angelini, Vincenzo Nigro

Research output: Contribution to journalArticle

Abstract

A large mutation screening of 504 patients with muscular dystrophy or myopathy has been performed by next generation sequencing (NGS). Among this cohort of patients, we report a case with a severe form of muscular dystrophy with a proximal weakness in the limb-girdle muscles. Her biopsy revealed typical dystrophic features and immunohistochemistry for α- and γ-sarcoglycans showed an absent reaction, addressing the clinical diagnosis toward a sarcoglycanopathy. Considering that no causative point mutation was detected in any of the four sarcoglycan genes, we re-evaluated the NGS data by careful quantitative analysis of the specific reads mapping on the four sarcoglycan genes. A complete absence of reads from the sixth exon of the β-sarcoglycan gene was found. Subsequent array comparative genomic hybridization (CGH) analysis confirmed the result with the identification of a novel 3.3 kb intragenic deletion in the SGCB gene. This case illustrates the importance of a multidisciplinary approach involving clinicians and molecular geneticists and the need for a careful re-evaluation of NGS data.

Original languageEnglish
JournalNeuromuscular Disorders
DOIs
Publication statusAccepted/In press - Oct 15 2015

Keywords

  • Copy number variation
  • Deletion
  • LGMD2E
  • Next generation sequencing
  • Sarcoglycanopathy
  • SGCB

ASJC Scopus subject areas

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

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