Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.
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PMID:Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease. 130 48

During a systematic chromosomal survey of 167 unrelated boys with the X-linked recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X) (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the subject's phenotypically normal mother, where it was preferentially inactivated. The restriction fragment length polymorphism and methylation patterns at DXS255 indicated that the rearrangement originated from the maternal grandfather. Together with a previously described X;autosomal translocation in a female Menkes patient, the present finding supports the localization of the Menkes locus (MNK) to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is compatible with linkage data in both man and mouse. The chromosomal bend associated with the X-inactivation center (XIC) was present on the proximal long arm of the rearranged X chromosome, in line with a location of XIC proximal to MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171, DXS56-MNK-PGK1-Xqter.
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PMID:Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an intrachromosomal insertion of the segment Xq13.3-q21.2. 134 49

The gene responsible for Menkes syndrome has been assigned to Xq13 by a combination of comparative mapping and linkage analysis. A previous report has mapped the translocation breakpoint associated with the disease in a female patient to an interval delimited by PGK1 and a group of six more proximal Xq13 markers, including DXS56. We have characterized a number of PGK1- or DXS56-positive YACs, from which we have generated six new markers. One of them identifies a small overlap region between a PGK1-positive YAC and three DXS56-positive YACs, distal to the Menkes breakpoint. A 560-kb region covered by a DXS56-positive YAC has been restriction-mapped and subcloned, disclosing a 187-kb MluI fragment astride the breakpoint. A probe mapping distal to the rearrangement in the same interval reveals altered PGFE fragments in a hybrid constructed from the translocation patient's DNA. We describe the development of a cosmid contig extending 150 kb from a nearby CpG island across the breakpoint. This contig includes four adjacent clones displaying cross-specific hybridization.
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PMID:Fine mapping and cloning of the breakpoint associated with Menkes syndrome in a female patient. 142 84

Linkage analyses were performed in 11 families with X-linked Menkes disease. In each family more than one affected patient had been diagnosed. Forty informative meioses were tested using 11 polymorphic DNA markers. From two-point linkage analyses high lod scores are seen for DXS146 (pTAK-8; maximal lod score 3.16 at recombination fraction [theta] = .0), for DXS1 (p-8; maximal lod score 3.44 at theta = .0), for PGK1 (maximal lod score 2.48 at theta = .0), and for DXS3 (p19-2; maximal lod score 2.90 at theta = .0). This indicates linkage to the pericentromeric region. Multilocus linkage analyses of the same data revealed a peak for the location score between DXS146(pTAK-8) and DXYS1X(pDP34). The most likely location is between DXS159 (cpX289) and DXYS1X(pDP34). Odds for this location relative to the second-best-supported region, between DXS146(pTAK-8) and DXS159 (cpX289), are better than 74:1. Visualization of individual recombinant X chromosomes in two of the Menkes families showed the Menkes locus to be situated between DXS159(cpX289) and DXS94(pXG-12). Combination of the present results with the reported absence of Menkes symptoms in male patients with deletions in Xq21 leads to the conclusion that the Menkes locus is proximal to DXSY1X(pDP34) and located in the region Xq12 to Xq13.3.
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PMID:Multipoint linkage analysis in Menkes disease. 157 Aug 30

Menkes syndrome is a rare X-linked recessive disorder characterized by an inability to metabolize copper. A female patient with both this disease and an X; autosome translocation with karyotype 46,X,t(X;2)(q13;q32.2) has previously been described. The translocation breakpoint in Xq13 coincides with a previous assignment of the Menkes gene at Xq13 by linkage data in humans and by analogy to the mottled mutations which are models for Menkes disease in the mouse. Therefore, this translocation probably interrupts the gene for Menkes syndrome in band Xq13. We describe here experiments to precisely map the translocation breakpoint within this chromosomal band. We have established a lymphoblastoid cell line from this patient and have used it to isolate the der(2) translocation chromosome (2pter----2q32::Xq13----Xqter) in human/hamster somatic cell hybrids. Southern blot analyses using a number of probes specific for chromosomes X and 2 have been studied to define precisely the location of the translocation breakpoint. Our results show that the breakpoint in this patient--and, therefore, likely the Menkes gene--maps to a small subregion of band Xq13.2-q13.3 proximal to the PGK1 locus and distal to all other Xq13 loci tested.
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PMID:Localization of the translocation breakpoint in a female with Menkes syndrome to Xq13.2-q13.3 proximal to PGK-1. 203 33

Menkes disease (MNK) lies immediately proximal to pphosphoglycerate kinase (PGK1) in Xq13 in human. Phenotypic similarities between MNK patients and murine mottled (Mo) mutants strongly suggest that both defects are caused by mutations at the same locus. Human MNK cDNA clones and a genomic subclone derived from a 40-kb YAC clone that includes Pgk1 have been used to position the murine homologue of Menkes disease (MNK, Mnk) immediately proximal to, and within 150-200 kb of, phosphoglycerate kinase (Pgk1) on the mouse X chromosome using interspecific backcross analysis and pulsed-field gel electrophoresis. A related autosomal locus has been mapped to mouse chromosome 18. RFLVs at Mnk between inbred strains of mice that show a strong association with the presence of the Mo phenotype have been detected. Hybridization of 4.1 kb of the 4.5-kb MNK coding sequence failed to reveal any deletions or alterations to restriction fragments containing exons of the Mnk locus in 9 Mo mutants. Furthermore, no genomic deletions or alterations > 20 kb were detected in 10 independently derived Mo mutants using pulsed-field gel electrophoresis. As no deletions or alterations at the Mnk gene were found, we suggest that any mutations in Mnk that cause the Mo phenotype are likely to be due to small changes at the nucleotide level and/or small deletions (< 20 kb) that lie outside the coding sequence.
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PMID:Analysis of Mnk, the murine homologue of the locus for Menkes disease, in normal and mottled (Mo) mice. 795 88

Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental retardation loci). Genes involved in the phenotypes have been isolated for only two of them (Menkes and SCIDX). It was therefore interesting to isolate and characterize new genes from the region. In a previous work (12 and Consalez et al, in preparation) we isolated a gene (XNP), located 350 Kb proximal to PGK1, potentially coding for a nuclear protein. We describe here the cloning and characterization of the murine homologue. The pattern of expression of the gene in the newborn mouse (especially the expression in particular regions of the brain: optical lobe, frontal cortex, hippocampus and cerebellum), as well as the expression in human tissues, suggests that this gene might be involved in neuronal differentiation. Among the different morbid phenotypes assigned to the region, X-linked mental retardation would be the best candidate to be associated with this gene.
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PMID:Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3. 816 50

We have used human/mouse hybrid cell lines to derive a pulsed-field map of the Xq13 region of the human X chromosome, in the vicinity of the X inactivation center (XIC). We have mapped nine loci within two separate clusters (I and II). Cluster I contains three loci (DXS227, XIST, and DXS128) linked within 1700 kb. This cluster also includes the breakpoint of a translocated X;14 chromosome used to define the proximal border of the XIC region. Cluster II covers an additional 1800 kb and physically links six loci (DXS56, DXS171, DXS325, DXS347, DXS356, and DXS441) located between the XIC and the genes for Menkes disease (MNK) and PGK1. Maps of cluster I loci derived from active (Xa) or inactive (Xi) X chromosomes differed, presumably due to methylation differences between the Xa and Xi. This map provides a basis for examining the organization of the Xq13.2-q13.3 region, in and around the XIC, and will assist in the further cloning of expressed sequences from this region.
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PMID:Pulsed-field map of Xq13 in the region of the human X inactivation center. 840 3