Arginine-164-tryptophan substitution in connexin32 associated with X linked dominant Charcot-Marie-Tooth disease.

Oterino, Agustı́n; Montón, Fernando; Cabrera, Vicente M.; Pinto, Francisco M.; Gonzalez, António; Lavilla, N R

doi:10.1136/jmg.33.5.413

Cited by 15 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Missense mutation Arg164Trp is present in the CMT Consortium Mutations Update database , although it has been described also by other authors [Ionasescu et al, 1996a;Oterino et al, 1996;Bort et al, 1997;Haites et al, 1998]. The remaining two mutations (Tyr151Ser; Pro184Leu) have been described only by us ( Table 2).…”

Section: Resultsmentioning

confidence: 82%

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families

et al. 2001

View full text Add to dashboard Cite

Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity. It is caused mainly by a 1.5 Mb duplication in 17p11.2, but also by mutations in the myelin genes PMP22 (peripheral myelin protein 22), MPZ (myelin protein zero), Cx32 (connexin 32; also called GJB1), and EGR2 (early growth response 2). In this study, we have screened 172 index cases of Italian families in which there was at least one subject with a CMT1 diagnosis for the duplication on 17p11.2 and mutations in these genes. Among 170 informative unrelated patients, the overall duplication frequency was 57.6%. A difference could be observed between the duplication frequency in familial cases (71.6%) and that observed in non-familial cases (36.8%). Among the non-duplicated patients, 12 were mutated in Cx32, four in MPZ, two in PMP22, and none in the EGR2. In the non-duplicated cases, the overall point mutation frequency for these genes was 25.0%. We describe the mutations identified, and consider possible genotype-phenotype correlation.

show abstract

Section: Resultsmentioning

confidence: 82%

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families

et al. 2001

View full text Add to dashboard Cite

show abstract

“…If this hypothesis is true, the higher mutation rate in these codons might suggest that these codons are frequently altered in Spanish CMT1 and CMT2 patients. In fact, an R164W substitution has recently been described in a large family segregating CMTX1 and originating from the Canary Islands (Oterino et al 1996). It could be argued that these patients may have a common ancestor.…”

Section: Discussionmentioning

confidence: 99%

“…However, the three codon 183 mutations are different and it can be inferred that they have a different genealogical origin. In the case of mutations at codon 164, two patients share the same R164Q amino acid change but the third patient, CMT-208, and the family described by Oterino et al (1996) carry another, different, amino acid substitution, R164W. The different electrophysiological phenotype associated with each mutation, involving an identical amino acid in both cases, CMT1 to amino acid R164 and CMT2 to R183, suggests two possible explanations: first, the position of R residues within the Cx32 protein sequence may have some physiological relevance, although both are located within the second extracellular domain; second, and more plausibly, the observed phenotypic differences might be due to the sex of the patients.…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies

et al. 1997

View full text Add to dashboard Cite

Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited peripheral neuropathies. The most prevalent mutations are a reciprocal 1.5-Mb duplication and 1.5-Mb deletion, respectively, at the CMT1A/HNPP locus on chromosome 17p11.2. Point mutations in the coding region of the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) or connexin 32 (Cx32) have been reported in CMT patients, including CMT type 1 (CMT1), CMT type 2 (CMT2) and Déjérine-Sottas neuropathy (DS) patients, and only in the coding region of PMP22 in HNPP families lacking a deletion. We have investigated point and small mutations in the MPZ, PMP22 and Cx32 genes in a series of patients of Spanish ancestry: 47 CMT patients without duplications, and 5 HNPP patients without deletions. We found 15 different mutations in 16 CMT patients (34%). Nine different mutations in ten patients were detected in the Cx32 gene, this being the most frequently involved gene in this series, whereas five mutations involved the MPZ gene and only one the PMP22 gene. Six out of nine nucleotide substitutions in the Cx32 gene involved two codons encoding arginine at positions 164 and 183, suggesting that these two codons may constitute two Cx32 regions prone to mutate in the Spanish population. Analysis of HNPP patients revealed a 5' splicing mutation in intron 1 of the PMP22 gene in a family with autosomal dominance, which confirms allelic heterogeneity in HNPP. Ectopic mRNA analysis on leukocytes suggests that this mutation might behave as a null allele.

show abstract

“…The absence of male-tomale transmission in large CMT pedigrees suggests X-linked disease (Hahn et al, 1990;Ionasescu, 1995). CMTX is mostly associated with mutations in exon 2 of the connexin 32 (C×32) gene mapped to chromosome Xq13 (Bergoffen et al, 1993a,b;Cherryson et al, 1994;Fairweather et al, 1994;Ionasescu et al, 1994Ionasescu et al, , 1996Orth et al, 1994;LeGuern et al, 1994;Bone et al, 1995;Nelis et al, 1996;Oterino et al, 1996;Tan et al, 1996;Schiavon et al, 996). The1,574-base pair (bp) cDNA of the C×32 gene encodes a 32-kDa protein, which is a member of the family of membrane-spanning proteins that assemble to form gap junctions (Kumar and Gilula, 1986).…”

Section: Introductionmentioning

confidence: 96%

Charcot-Marie-Tooth disease with intermediate motor nerve conduction velocities: Characterization of 14 C×32 mutations in 35 families

Rouger

LeGuern

Birouk³

et al. 1997

Hum. Mutat.

View full text Add to dashboard Cite

Arginine-164-tryptophan substitution in connexin32 associated with X linked dominant Charcot-Marie-Tooth disease.

Cited by 15 publications

References 16 publications

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families

Mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies

Charcot-Marie-Tooth disease with intermediate motor nerve conduction velocities: Characterization of 14 C×32 mutations in 35 families

Contact Info

Product

Resources

About