Screening For Mutations In The Peripheral Myelin Genes PMP22, MPZ AND CX32 (GJB1) in Russian Charcot‐Marie‐Tooth Neuropathy Patients

Abstract

Charcot-Marie-Tooth disease (CMT) and related inherited peripheral neuropathies, includingDejerine-Sottas syndrome, congenital hypomyelination, and hereditary neuropathy with liability to pressure palsies (HNPP), are caused by mutations in three myelin genes: PMP22, MPZ and Cx32 (GJB1). The most common mutations are the 1.5 Mb CMT1A tandem duplication on chromosome 17p11.2-p12 in CMT1 patients and the reciprocal 1.5 Mb deletion in HNPP patients. We performed a mutation screening in 174 unrelated CMT patients and three HNPP families of Russian origin. The unrelated CMT patients included 108 clinically and electrophysiologically diagnosed CMT1cases, 32 CMT2 cases, and 34 cases with unspecified CMT. Fifty-nine CMT1A duplications were found, of which 58 belonged to the CMT1 patient group. We found twelve distinct mutations in Cx32, six mutations in MPZ, and two mutations in PMP22. Of these respectively, eight, five, and two lead to a CMT1 phenotype. Eight mutations (Cx32: Ile20Asn/ Gly21Ser, Met34Lys, Leu90Val, and Phe193Leu; MPZ: Asp134Gly, Lys138Asn, and Thr139Asn; PMP22: ValSer25-26del) were not reported previously. Phenotype-genotype correlations were based on nerve conduction velocity studies and mutation type. Hum Mutat 15:340-347, 2000.

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

“…However, the results were similar to those of Italian (57.6%) (Mostacciuolo et al, 2001) and Russian (53.7%) (Mersiyanova et al, 2000b).…”

“…We first examined the CMT1A duplication by genotyping seven microsatellites within the 17p11.2-p12 region, and found 15 CMT1A duplication families among 28 CMT1 cases. The duplication frequency (53.6%) in Korean patients is slightly lower than, or similar to those of European CMT1 cases: 70.7% in an Europian collaborative study , 57.6% in Italy (Mostacciuolo et al, 2001) and 53.7% in Russia (Mersiyanova et al, 2000b). However the frequency is higher than the level of 31.2% in Japanese CMT1 patients (Ikegami et al, 1997).…”

“…The p.Arg164Gln mutation was observed in an isolated CMT2 patient. Several previous studies have reported this mutation mostly in CMT1 demyelinating patients (Mersiyanova et al, 2000b;Yoshihara et al, 2000;Huehne et al, 2003). The c.30C>T (p.Leu10Leu) mutation was detected in two CMT patients, but not detected in the 105 controls.…”

Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease

“…The X-linked form of CMT (CMTX) is the second most frequent form of CMT (Ionasescu et al 1995;Nelis et al 1996;Mersiyanova et al 2000;Mostacciuolo et al 2001;Hattori et al 2003;Casasnovas et al 2006) and is associated with a large number of mutations in the gap junction beta 1 (GJB1) gene on chromosome Xq13 encoding the gap junction protein Connexin 32 (Cx32) (Bergoffen et al 1993;Shy et al 2007). Cx32 is expressed by Schwann cells and oligodendrocytes.…”

Hereditary neuropathy with liability to pressure palsies (HNPP) patients of Korean ancestry with chromosome 17p11.2-p12 deletion

“…To extract DNA from the buccal swabs, we used the phenol:chloroform:isoamylalcohol method after proteinase K treatment at a final concentration of 0.3 mg/ml at 55 o C for 3 h. The six (CA)n repeat microsatellite markers (D17S122, D17S921, D17S955, D17S839, D17S261 and D17S 1358) localized in the duplication/deletion region of chromosome 17p11.2-p12 were amplified by PCR. The primer sequences for PCR amplification were as described by Mersiyanova et al (2000). The genetic distance, primer sequences, annealing temperatures and PCR sizes are summarized in Table 1.…”