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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A contiguous set of 43 overlapping yeast artificial chromosome (YAC) clones has been developed for the Charcot-Marie-Tooth disease type 1A (CMT1A) duplication region of chromosome 17p11.2. The contig spans approximately 2.0 Mb and can be represented in a minimum of five overlapping YACs. The YAC clones were isolated from two total human genomic YAC libraries and from YAC libraries made from rodent-human hybrid cell lines. YAC clones were isolated from the libraries by polymerase chain reaction (PCR) technique. Localization to chromosome 17p11.2 was confirmed by fluorescence in situ hybridization. Overlap between the YAC clones was detected by inter-Alu PCR amplification of the YACs and by cross hybridization of the YACs with YAC insert ends obtained by Vectorette PCR. This YAC contig is a useful resource for analyzing and mapping all the genes contained within the CMT1A duplication.
Hum Mol Genet 1992 Nov
PMID:A yeast artificial chromosome contig spanning the Charcot-Marie-Tooth disease type 1A duplication region. 130 Nov 69

A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1.9 cM proximal to the Trp53 locus and by the finding, by others, that it codes for a myelin protein and that a point mutation in its fourth putative transmembrane region is associated with the trembler mutation. We have isolated the human homologous of the mouse Gas-3 gene and utilized the cloned sequences as a probe to localize the gene on human chromosomes both by analysis of human-rodent somatic cell hybrids and in situ hybridization of human metaphases. We have now localized the human Gas-3 gene on chromosome 17p12-13. Its possible role in both the development of neoplasia in neurofibromatosis patients and in the myelin degenerative disease as the Charcot-Marie-Tooth is discussed.
Hum Mol Genet 1992 Aug
PMID:Isolation and mapping to 17p12-13 of the human homologous of the murine growth arrest specific Gas-3 gene. 130 10

P0, the major structural protein of peripheral myelin, is a homophilic adhesion molecule with a single immunoglobulin (Ig) domain, which contains a single N-linked glycosylation site and two cysteines. We have previously reported four different mutations of the myelin P0 gene in four families of Charcot-Marie-Tooth neuropathy type 1 (CMT1). In this study we found a new mutation of the myelin P0 gene in a small family of CMT1. The affected persons had an A - to - G substitution of nucleotide 245 of the myelin P0 gene in one allele, leading to a cysteine substitution for tyrosine82 in the extracellular Ig-domain. An additional cysteine in the extracellular domain may form a disulfide bond and cause an inappropriate change in the tertiary structure of the functional Ig-domain of P0.
Biochem Mol Biol Int 1993 Sep
PMID:New mutation of the myelin P0 gene in a pedigree of Charcot-Marie-Tooth neuropathy 1. 750 51

We have characterized the human gene encoding the major peripheral myelin protein zero (P0) and assigned it, by in situ hybridization, to the q21.3-q23 region of human chromosome 1. This region is known to contain a cluster of interspersed genes coding for the related human leukocyte receptors of the Fc portion of the immunoglobulin G (Fc gamma RI, II, III). This colocalization was refined by the finding of a yeast artificial chromosome (YAC) of the Centre d'Etude du Polymorphisme Humain (CEPH) library, hybridizing to the P0 and Fc gamma RIIA genes, demonstrating their physical linkage. These data may have important implications in demyelinating diseases studies like Charcot-Marie-Tooth disease type 1B (CMT1B).
Hum Mol Genet 1993 Dec
PMID:The major peripheral myelin protein zero gene: structure and localization in the cluster of Fc gamma receptor genes on human chromosome 1q21.3-q23. 750 28

We have previously reported that the mutations of the myelin P0 gene were completely linked with Charcot-Marie-Tooth neuropathy type 1B (CMT1B) in two families. In this study we found a different mutation in another family with CMT1B. The mutation, a methionine substitution for isoleucine at amino acid position 30, is located in the extracellular domain, which constitutes an immunoglobulin domain responsible for the function of P0 as an adhesion molecule. The results confirmed that P0 is a gene responsible for CMT1B.
Hum Mol Genet 1993 Sep
PMID:Mutation of the myelin P0 gene in Charcot-Marie-Tooth neuropathy type 1B. 769 26

Collectively, the inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), the X chromosome (CMTX) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5 megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX) is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type II (CMT2) is an axonal neuropathy, also of undetermined cause. One form of CMT2 maps to chromosome 1p36 (CMT2A). Dejerine-Sottas disease, also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile onset demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene of the P0 gene. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5 Mb deletion in chromosome 17p11.2-12 and may result from reduced expression of the PMP22 gene. CMT1A and HNPP are apparent reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis.
Hum Mol Genet 1994
PMID:Molecular genetics of Charcot-Marie-Tooth disease and related neuropathies. 784 45

Charcot-Marie-Tooth disease type 1A (CMT1A) is a common autosomal dominant demyelinating neuropathy that is associated with a 1.5 megabase (Mb) tandem DNA duplication in chromosome 17p11.2-p12. Hereditary neuropathy with liability to pressure palsies (HNPP, tomaculous neuropathy) is another less frequently diagnosed autosomal dominant neuropathy and is associated with a 1.5 Mb deletion in chromosome 17p11.2-12. Meiotic unequal crossover is a proposed mechanism for the generation of both the duplication in CMT1A and the deletion in HNPP. CMT1A-REP is a repeat that flanks the region which is duplicated/deleted in CMT1A/HNPP. The CMT1A-REP repeat sequence may mediate unequal crossover through misalignment of the homologous, repeated sequences. Three copies of the CMT1A-REP repeat are present on stably inherited CMT1A duplication chromosomes. In this report, molecular analysis in multiple patients detected three copies of the CMT1A-REP sequence on both inherited and de novo CMT1A duplication chromosomes, and one copy of the CMT1A-REP repeat on the deleted chromosome in both inherited and de novo HNPP. These observations support the hypothesis that a reciprocal recombination mechanism involving the CMT1A-REP is responsible for the generation of both the duplicated and deleted chromosomes, and document the first examples in humans of Mendelian syndromes resulting from the reciprocal products of unequal exchange involving large intra-chromosomal segments.
Hum Mol Genet 1994 Feb
PMID:Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17. 800 87

We studied a family with nine of twenty members affected with Charcot-Marie-Tooth disease type 1A (CMT1A). The proband and her four affected sibs showed no duplication of the 17p11.2-p12 (CMT region). Two of the proband's affected daughters and three affected grandchildren showed duplication of the PMP-22 gene and of the marker VAW409R3 but not of the markers VAW412R3 and EW401. Pulsed field gel electrophoresis (PFGE) revealed a 220 kb SacII fragment in one CMT1A patient with duplication instead of a 500 kb SacII fragment as previously reported (1, 3, 4, 6-9). Our findings suggest a smaller size of the duplication in this CMT1A family. The disease segregates with the same haplotype in both duplicated and nonduplicated CMT1A patients. The clinical phenotype showed more severe weakness with earlier onset and motor nerve conduction velocities were characterized by more significant slowing in the patients with duplication than in the patients who did not show duplication.
Hum Mol Genet 1993 Apr
PMID:Charcot-Marie-Tooth neuropathy type 1A with both duplication and non-duplication. 809 3

A 1.5 Mb duplication within 17p11.2 is the major mutation causing both autosomal dominant and sporadic Charcot-Marie-Tooth disease type 1A (CMT1A). An independent origin for the mutation in each family has been postulated. The proposed genetic mechanism causing the CMT1A duplication is unequal nonsister chromatid exchange at meiosis (unequal crossing-over). We studied the parental origin of the duplication in nine genetically sporadic CMT1A patients and demonstrated that in all cases the mutation was the product of an unequal nonsister chromatid exchange during spermatogenesis. The fact that only paternal de novo duplications were observed in the sporadic CMT1A patients suggests that male specific factors may be operating during spermatogenesis that either help forming the duplication and/or stabilize the duplicated chromosome.
Hum Mol Genet 1993 Dec
PMID:Origin of the de novo duplication in Charcot-Marie-Tooth disease type 1A: unequal nonsister chromatid exchange during spermatogenesis. 811 70

X-linked dominant Charcot-Marie-Tooth disease (CMTX1) is a peripheral neuropathy which maps to Xq13 and is flanked by the loci DXS106 (Xq11.2-q12) and DXS559 (Xq13.1). Contained within this interval of approximately 2-3Mb of DNA is the gene, connexin 32 (locus designation GJ beta 1). This gene encodes a gap junction protein which is expressed in large quantities within the liver and throughout a range of other mammalian tissues. We have sequenced the coding region of exon 2 of this gene from affected individuals in nine families with CMTX 1 and have found mutations which segregate with the disease in eight of these families. The mutations detected include missense point mutations at codons 15, 60, 63, 208, and 215, a nonsense point mutation at codon 220, deletions of one base in codon 72/3 producing a stop codon 12 codons down stream and a three base pair deletion which can be predicted to result in the loss of a single amino acid. These findings are consistent with the disease CMTX1 being the result of mutations affecting the gene connexin 32 (Cx32).
Hum Mol Genet 1994 Jan
PMID:Mutations in the connexin 32 gene in X-linked dominant Charcot-Marie-Tooth disease (CMTX1) 816 49


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