Mutational analysis ofPMP22, MPZ, GJB1, EGR2 andNEFL in Korean Charcot-Marie-Tooth neuropathy patients

Abstract

We examined CMT1A duplication of 17p11.2-p12, mutations of PMP22, MPZ (P0), GJB1 (Cx32), EGR2 and NEFL genes in 57 Korean families with patients diagnosed as having Charcot-Marie-Tooth (CMT) disease. The CMT1A duplication was present in 53.6% of 28 CMT type 1 patients. In the 42 CMT families without CMT1A duplication, 10 pathogenic mutations were found in 9 families. The 10 mutations were not detected in 105 healthy controls. Seven mutations ( c.318delT (p.Ala106fs) in PMP22, c.352G>A (p.Asp118Asn), c.449-1G>T (3'-splice site), c.706A>G (p.Lys236Glu) in MPZ, c.408T>C (p.Val136Ala), c.502T>C (p.Cys168Arg) in GJB1, and c.1001T>C (p.Leu334Pro) in NEFL) were determined to be novel. The mutation frequencies of PMP22 and MPZ were similar to those found in several European populations, however, it appeared that mutations in GJB1 are less frequent in East Asian CMT patients than in European patients. We described the identified mutations and phenotype-genotype correlations based on nerve conduction studies.

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

“…Table 1 shows that five unrelated patients were heterozygotes of the following missense mutations: Pro8Leu (c.23C4T), 8 Asn98Ser (c.293A4G), 8,10 Glu90Lys (c.268G4A) 8 and Glu396Lys (c.1186G4A). 11,12 One patient (case 2) was a homozygote of a novel nonsense mutation, Glu140Stop (c.418G4T), who was born to consanguineous parents and who had a similarly affected brother. All patients except for case 2 were sporadic.…”

NEFL Pro22Arg mutation in Charcot-Marie-Tooth disease type 1

“…The mutation was screened by DNA sequencing of all exons and contiguous flanking intronic sequences. The primer sequences and polymerase chain reaction (PCR) conditions of 17p11.2-p12 duplication/deletion, NEFL, Cx32, EGR2, MPZ, and PMP22 were followed by Choi et al (2004), and PCR conditions of DNM2, MFN2, HSP27, or HSP22 genes are available on request. PCR products were purified using EXOSAP-IT kits (USB, USA), and nucleotide sequences were determined using an automatic genetic analyzer ABI3100 using a big dye terminator cycle sequencing ready reaction kit (Applied Biosystems, USA).…”

Prenylation-Defective Human Connexin32 Mutants Are Normally Localized and Function Equivalently to Wild-Type Connexin32 in Myelinating Schwann Cells

“…However, despite the large number of different mutations, the clinical severity caused by different mutations appears to be relatively uniform in affected men, including those with a deleted gene. Some mutations appear to cause exceptionally severe phenotypes, typically with early onset: R22stop Birouk et al, 1997), the double-mutation R22Q and V63I (Silander et al, 1998), V136A (Choi et al, 2004), 147 frameshift (Meggouh et al, 1998), C201R (Sillen et al, 1998), F235C (Lin et al, 1999), and the deletion nucleotides 265-273 deletion/frameshift . E102G, N175D, and T191A have been reported to be associated with a milder phenotype (Silander et al, 1998;Kobari et al, 2000;Abrams et al, 2003).…”