title: Identification of Genetic Causes of Inherited Peripheral Neuropathies by Targeted Gene Panel Sequencing.
abstract: Inherited peripheral neuropathies (IPN), which are a group of clinically and genetically heterogeneous peripheral nerve disorders including Charcot-Marie-Tooth disease (CMT), exhibit progressive degeneration of muscles in the extremities and loss of sensory function. Over 70 genes have been reported as genetic causatives and the number is still growing. We prepared a targeted gene panel for IPN diagnosis based on next generation sequencing (NGS). The gene panel was designed to detect mutations in 73 genes reported to be genetic causes of IPN or related peripheral neuropathies, and to detect duplication of the chromosome 17p12 region, the major genetic cause of CMT1A. We applied the gene panel to 115 samples from 63 non-CMT1A families, and isolated 15 pathogenic or likely-pathogenic mutations in eight genes from 25 patients (17 families). Of them, eight mutations were unreported variants. Of particular interest, this study revealed several very rare mutations in the SPTLC2, DCTN1, and MARS genes. In addition, the effectiveness of the detection of CMT1A was confirmed by comparing five 17p12-nonduplicated controls and 15 CMT1A cases. In conclusion, we developed a gene panel for one step genetic diagnosis of IPN. It seems that its time- and cost-effectiveness are superior to previous tiered-genetic diagnosis algorithms, and it could be applied as a genetic diagnostic system for inherited peripheral neuropathies.
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju 32588, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Nam
authors.affiliation: Stem Cell & Regenerative Medicine Center and Neuroscience Center, Samsung Medical Center, Seoul 06351, Korea.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju 32588, Korea.
authors.forename: Young Se
authors.initials: YS
authors.lastname: Hyun
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju 32588, Korea.
authors.forename: Da Eun
authors.initials: da E
authors.lastname: Nam
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Tech., Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Geon
authors.initials: G
authors.lastname: Kwak
authors.affiliation: Department of Neurology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Stem Cell & Regenerative Medicine Center and Neuroscience Center, Samsung Medical Center, Seoul 06351, Korea.|Department of Neurology, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Tech., Sungkyunkwan University, Seoul 06351, Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Kongju National University, Gongju 32588, Korea.
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
mesh_terms: D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D000072159:Dynactin Complex / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D009154:Mutation; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D056910:Republic of Korea; D017422:Sequence Analysis, DNA / Q000379:methods*; D051102:Serine C-Palmitoyltransferase / Q000235:genetics
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; C495089:SPTLC2 protein, human; D051102:Serine C-Palmitoyltransferase
keywords: DCTN1; MARS; SPTLC2; charcot-Marie-Tooth disease (CMT); gene panel; inherited peripheral neuropathy