Myelin protein zero (MPZ) gene mutations in nonduplication type 1 Charcot-Marie-Tooth disease

Roa, Benjamin B.; Warner, Laura E.; García, Carlos; Russo, Donna; Lovelace, Robert E.; Chance, Phillip F.; Lupski, James R.

doi:10.1002/(sici)1098-1004(1996)7:1<36::aid-humu5>3.0.co;2-n

Cited by 60 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In patient CMT-252 the mutation detected alters the consensus 3′ or acceptor splice site of the third intron of the MPZ gene. This is the first splice-site mutation reported in the MPZ gene associated with demyelinating inherited neuropathies (Hayasaka et al 1993 a, c;Kulkens et al 1993;Nelis et al 1994a, b;Latour et al 1995;Roa et al 1996).…”

Section: Discussionmentioning

confidence: 97%

“…These abnormal bands did not segregate with the disease within the families. Two of them involved the MPZ gene and have previously been described: a C to T silent mutation in codon G200 in exon 5 (Roa et al 1996), and a C to T mutation at codon S228 in exon 6 (Nelis et al 1994a). Three novel changes were detected in normal relatives of two patients, suggesting that they are nonpathological polymorphisms or recessive mutations: a G to T transversion in MPZ gene exon 6, which produces an R to L amino acid change at codon 244, and two different changes at PMP22 gene exon 4 in relatives of a DS patient, one silent mutation that did not modify the C residue at codon 109 in the father, and an I137V substitution in the unaffected mother and sister.…”

Section: Mpz and Pmp22 Polymorphismsmentioning

confidence: 99%

See 1 more Smart Citation

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

Section: Discussionmentioning

confidence: 97%

Section: Mpz and Pmp22 Polymorphismsmentioning

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

show abstract

“…The primers for exons 1, 2, 3, 4 and 6 have been as described by Nelis et al [7] and for exon 5 by Roa et al [10]. Each amplified segment was sequenced directly in both directions using an ABI Dye Primer Cycle Sequencing Ready Reaction Kit with AmpliTaq DNA Polymerase, FS (PE applied Biosystems) and electrophoresed in a 6% acrylamide gel in an automated ABI 373A DNA Sequencer (PE applied Biosystems).…”

Section: P0 Sequencing Analysesmentioning

confidence: 99%

Phenotypic variation of a new P0 mutation in genetically identical twins

Marques

Hanna

Marques

et al. 1999

Journal of Neurology

View full text Add to dashboard Cite

We have identified a new point mutation in the myelin protein zero (P0) gene in two genetically identical twins with a demyelinating neuropathy. The G to A transition at nucleotide position 382 caused an aspartic acid to asparagine substitution in exon 3. Moreover, we found clear clinical differences which were most evident at an early age. These observations suggest that the expression of this P0 mutation may be susceptible to external, non-genetic influences that may act early in the course of the disease to alter the phenotype.

show abstract

“…a). This mutation affected an amino acid conserved by evolution and other mutations at the same codon, p.G108S, p.G108A and p.G108D have been previously described to cause a dominant demyelinating neuropathy. Moreover, the identified MPZ variant was excluded in 612 Italian control chromosomes.…”

Section: Pathological Findingsmentioning

confidence: 91%

Sural nerve biopsy and functional studies support the pathogenic role of a novel MPZ mutation

et al. 2014

View full text Add to dashboard Cite

Our patient is a 65-year-old woman presenting with bilateral pes cavus, pronounced distal muscle wasting, weakness and areflexia. Electrophysiological findings included diffuse unrecordable motor and sensory responses. While the CMT phenotype was evident, the lack of family history and the severe, but unspecific electrophysiological impairment, was a challenge for genetic diagnosis. A sural nerve biopsy was performed, showing a severe loss of myelinated fibers with residual axons surrounded by myelin outfoldings. Whereas myelin outfoldings are a pathological hallmark of autosomal recessive CMT4B1 and CMT4B2, due to mutations in myotubularin-related 2 (MTMR2) and 13 (MTMR13) genes respectively, they may also occur in nerve biopsies from CMT1B patients. By direct sequencing, a novel heterozygous transversion c.410G>T in MPZ gene was demonstrated, producing an amino acid change from glycine to valine in position 108 (p.G108V). In HeLa cells the fusion P0G108V-EGFP was normally trafficked to the cell membrane, but with decreased P0 adhesion function, compared with wild-type P0, thus supporting a pathogenic role of the new variant. In conclusion this case highlights the relevance, in selected cases, of sural nerve biopsy to orient the genetic/molecular tests, while in vitro analyses may strengthen the pathogenic role of novel mutations.

show abstract

Myelin protein zero (MPZ) gene mutations in nonduplication type 1 Charcot-Marie-Tooth disease

Cited by 60 publications

References 33 publications

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

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

Phenotypic variation of a new P0 mutation in genetically identical twins

Sural nerve biopsy and functional studies support the pathogenic role of a novel MPZ mutation

Contact Info

Product

Resources

About