The allelic spectrum of Charcot–Marie–Tooth disease in over 17,000 individuals with neuropathy

Autor:	Khalida Liaquat, Izabela Karbassi, Matthew C. Evans, Sat Dev Batish, James R. Lupski, Jeremiah R Jones, Malgorzata Jaremko, Michelle York, Crystal M Bishop, Corey D. Braastad, Christopher Elzinga, Adam C. Medeiros, Carol Hoffman, Zhenyuan Wang, Joseph Higgins, Christina DiVincenzo
Rok vydání:	2014
Předmět:	Genetics Sanger sequencing Mutation peripheral neuropathy medicine.diagnostic_test Original Articles Charcot–Marie–Tooth disease Biology medicine.disease_cause molecular epidemiology Molecular biology genetic testing Frameshift mutation symbols.namesake symbols medicine Missense mutation Multiplex ligation-dependent probe amplification high-throughput nucleotide sequencing Allele Molecular Biology Gene Genetics (clinical) Genetic testing
Zdroj:	Molecular Genetics & Genomic Medicine
ISSN:	2324-9269
DOI:	10.1002/mgg3.106
Popis:	We report the frequency, positive rate, and type of mutations in 14 genes (PMP22, GJB1, MPZ, MFN2, SH3TC2, GDAP1, NEFL, LITAF, GARS, HSPB1, FIG4, EGR2, PRX, and RAB7A) associated with Charcot-Marie-Tooth disease (CMT) in a cohort of 17,880 individuals referred to a commercial genetic testing laboratory. Deidentified results from sequencing assays and multiplex ligation-dependent probe amplification (MLPA) were analyzed including 100,102 Sanger sequencing, 2338 next-generation sequencing (NGS), and 21,990 MLPA assays. Genetic abnormalities were identified in 18.5% (n = 3312) of all individuals. Testing by Sanger and MLPA (n = 3216) showed that duplications (dup) (56.7%) or deletions (del) (21.9%) in the PMP22 gene accounted for the majority of positive findings followed by mutations in the GJB1 (6.7%), MPZ (5.3%), and MFN2 (4.3%) genes. GJB1 del and mutations in the remaining genes explained 5.3% of the abnormalities. Pathogenic mutations were distributed as follows: missense (70.6%), nonsense (14.3%), frameshift (8.7%), splicing (3.3%), in-frame deletions/insertions (1.8%), initiator methionine mutations (0.8%), and nonstop changes (0.5%). Mutation frequencies, positive rates, and the types of mutations were similar between tests performed by either Sanger (n = 17,377) or NGS (n = 503). Among patients with a positive genetic finding in a CMT-related gene, 94.9% were positive in one of four genes (PMP22, GJB1, MPZ, or MFN2).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::328d58bde16897d10ff30c4bd94f7e27 https://doi.org/10.1002/mgg3.106 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.