Identification of an intragenic deletion in the SGCB gene through a re-evaluation of negative next generation sequencing results.
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.
Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Napoli, Italy; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Teresa
T
Giugliano
Dipartimento di Neuroscienze, Università di Padova, Padova, Italy.
Marina
M
Fanin
Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Napoli, Italy; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Marco
M
Savarese
Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Napoli, Italy.
Giulio
G
Piluso
Fondazione Ospedale S. Camillo, IRCCS, Venice, Italy.
Corrado
C
Angelini
Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Napoli, Italy; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy. Electronic address: vinnigro@gmail.com.
Vincenzo
V
Nigro
D002648:Child; D055028:Comparative Genomic Hybridization; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D046228:Microarray Analysis; D058088:Sarcoglycanopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049031:Sarcoglycans / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
C483098:SGCB protein, human; D049031:Sarcoglycans
Copy number variation; Deletion; LGMD2E; Next generation sequencing; SGCB; Sarcoglycanopathy