The major peripheral myelin protein zero gene: structure and localization in the cluster of <i>Fcγ</i> receptor genes on human chromosome 1q21.3 – q23

Objectives-To determine the molecular basis for autosomal dominant intermediate hereditary motor and sensory neuropathy (HMSN) in a four generation family. The gene defects in families with intermediate HMSN are not known, but it has been suggested that most have X linked HMSN. Methods-All participating family members were examined clinically. Genomic DNA was obtained from 10 aVected and seven unaVected members. Linkage analysis for the known HMSN loci was first performed. Mutations in the peripheral myelin protein zero gene (PMP0) were sought in two aVected members, using one unaVected member for comparison, by amplification of the six exons of the gene followed by single strand conformation polymorphism (SSCP) analysis, dideoxy fingerprinting (ddF), and sequencing. Subsequently, the mutation was screened for in all aVected and unaVected members in the family using Alu I digestion and in 100 unrelated control subjects using "snap back" SSCP analysis. Sequencing of cDNA from a sural nerve biopsy from an aVected member was also performed. Results-The clinical phenotype was of variable severity, with motor nerve conduction velocities in the intermediate range. Linkage to PMP0 was demonstrated. Analysis of genomic DNA and cDNA for PMP0 identified a novel codon 35 GAC to TAC mutation. The mutation produces an inferred amino acid change of aspartate to tyrosine at codon six of the processed protein (Asp6Tyr) in the extracellular domain and was present in all aVected family members but not in 100 unrelated controls. Conclusions-The present findings further extend the range of phenotypes associated with PMP0 mutations and indicate that families with "intermediate" HMSN need not necessarily be X-linked as previously suggested. (J Neurol Neurosurg Psychiatry 1999;67:174-179)

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“… 1-150 Taken from Nelis et al 24 1-151 GDB primer M49 - http://gdbwww.gdb.org The others were picked from the sequence in Pham-Dinh et al 25 …”

Section: Methodsmentioning

confidence: 99%

Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy

Mastaglia

Nowak

Stell

et al. 1999

Journal of Neurology, Neurosurgery & Psychiatry

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“…1; see Shapiro et al, 1996). The 7-kb human gene maps to chromosome position 1q22-23 and is split into six exons by five introns (Hayasaka et al, 1993b;Pham Dinh et al, 1993). It was predicted from the primary sequence (Lemke and Axel, 1985) and has been experimentally verified (D'Urso et al, 1990) that P 0 is a single-pass integral membrane glycoprotein synthesized as a polypeptide precursor with a cleavable amino terminus signal sequence.…”

Section: Molecular and Structural Characterizationmentioning

confidence: 99%

Myelin protein zero and membrane adhesion

Spiryda

1998

J. Neurosci. Res.

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Protein zero (P0) is a member of the immunoglobulin gene superfamily (IgCAM) that is expressed at high levels in myelinated vertebrates in central (fish and amphibia) and peripheral (all species) myelin. This glycoprotein is the major adhesive component of peripheral myelin, where it mediates self-adhesion of the Schwann cell plasma membrane. Although the expression of P0 is naturally limited to Schwann cells, the molecular mechanisms of P0-mediated adhesion can be considered general and "obligatory" because, when expressed in a variety of cell lines, P0 induces strong intercellular adhesion. Modeling studies, X-ray crystallographic analysis, and experimental site-directed mutagenesis have provided excellent working models for understanding how P0 mediates adhesion at the atomic level. These models remain to be experimentally tested. However, in humans, certain mutations in P0 produce dysmyelinating disease, possibly due to disruptions in the predicted P0 lattice.

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“…It can also maintain the compacted state of mature myelin through its intracellular portion, which has two tyrosine phosphorylation sites resembling ITIM sequence. 21 In addition, myelin P0 shows strong pathological implications and its mutations account for a variety of inherited human peripheral neuropathies, including Charcot-Marie-Tooth disease type 1B 22 and Dejerine-Scottas syndrome. 23 It is reasonable, therefore, to presume that MPZL1/ PZR plays a similar role in mediating cell-cell interactions in a variety of cells.…”

Section: Discussionmentioning

confidence: 99%

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese

Liu

Qin

et al. 2006

Mol Psychiatry

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The MPZL1/PZR gene has been mapped to 1q23.3, located in close proximity to a recognized schizophrenia susceptibility locus. Recently, the MPZL1/PZR gene has been found to be significantly upregulated in schizophrenia brain tissue and to play an important role in cell signaling, thus indicating that MPZL1/PZR could be a potential schizophrenia marker. To test this hypothesis, we selected three single nucleotide polymorphisms (SNPs) for genotyping in 523 Han Chinese trios. We found that two individual SNPs were significant at the Bonferroni's corrected significance level P < 0.017: rs3767444 (v 2 = 6.299, P = 0.0121) and rs2051656 (v 2 = 9.856, P = 0.0017). Haplotype transmission/disequilibrium tests revealed a significant association with the disease (global P-value = 1.064 Â 10 À6 ), but no specific transmission distortions. Thus, we propose that the MPZL1/PZR gene may be important in the predisposition to schizophrenia among Han Chinese.

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The major peripheral myelin protein zero gene: structure and localization in the cluster of Fcγ receptor genes on human chromosome 1q21.3 – q23

Cited by 32 publications

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Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy

Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy

Myelin protein zero and membrane adhesion

MPZL1/PZR, a novel candidate predisposing schizophrenia in Han Chinese

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