Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown clinical benefit resulting from recombinant interferon gamma (rIFN-gamma) therapy in patients affected by chronic granulomatous disease (CGD), which represents an important adjunct to conventional therapy. In order to evaluate the effect of interferon gamma therapy, we investigated clinical and haematological parameters in a child with X-linked CGD, McLeod phenotype (kell negative) and hyper-IgE, before and after 8 months of therapy. Our results show no significant effect of rIFN-gamma on the respiratory burst of peripheral polymorphonuclear leukocytes. This notwithstanding, we observed improved clinical and haematological conditions. These results support the view that interferon gamma may benefit these subjects by influencing oxygen-independent antimicrobial activity or other immunological parameters.
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PMID:Successful interferon gamma therapy in a patient with X-linked chronic granulomatous disease, McLeod syndrome and hyper-IgE. Case report. 808 23

X-linked retinitis pigmentosa (XLRP) is characterized by retinal degeneration with night blindness and progressive reduction of the visual fields. By linkage and deletion analysis a gene locus (RP3) has been mapped to the short arm of the X chromosome between the genes CYBB and OTC. Analysis of transcript in this region has revealed a gene which is abundantly expressed in human retina and encodes a putative membrane protein with significant homologies to short consensus repeat (SCR/sushi) domains known from selections and complement proteins. The gene termed SRPX (sushi-repeat-containing protein, x chromosome) is deleted in an RP patient who also suffers from chronic granulomatous disease and McLeod syndrome. A 75 kb deletion removing exon 1 of the gene was also found in two brothers of a second XLRP family. However, no further functionally significant mutations were detected by SSCP screening of all 10 exons in 34 unrelated XLRP patients nor by full length RT-PCR sequencing in two RP3 families. The role of this highly conserved retinal gene in the pathogenesis of RP therefore remains to be determined.
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PMID:A gene (SRPX) encoding a sushi-repeat-containing protein is deleted in patients with X-linked retinitis pigmentosa. 863 8

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was thought to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending approximately 3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located approximately 40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected mate shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3.
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PMID:A recombination outside the BB deletion refines the location of the X linked retinitis pigmentosa locus RP3. 865 20

The 22 antigens of the Kell blood group system are located on a red blood cell (RBC) membrane glycoprotein that shows sequence homology with a family of metalloendopeptidases. Expression of the Kell system antigens is partially governed by XK, an X-linked gene that encodes the Kx protein; absence of Kx results in reduced Kell antigen expression. Almost total absence of Kell antigens from the RBCs of a German man with no symptoms of neuroacanthocytosis could not be due to the Kell-null phenotype, Ko, because his RBCs had very weak expression of Kx antigen and his three children were Kp(a + b+). Kell antigens were normal on the RBCs of his son but weak on those of his two daughters. An Nla III restriction fragment-length polymorphism within the KEL gene showed the Kpa/Kpa genotype in the propositus. Sequencing of his XK gene showed a single base change within the donor splice consensus sequence of intron 2. A BsaAl restriction fragment-length polymorphism showed the mutation in both of his daughters but not in his son. The extreme depression of the Kell antigens of the propositus must be due to a combination of effects, ie, homozygosity for Kpa and deficiency of Kx protein, each of which is capable of causing some degree of weakening of Kell antigens.
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PMID:A combination of the effects of rare genotypes at the XK and KEL blood group loci results in absence of Kell system antigens from the red blood cells. 891 72

The gene responsible for X-linked retinitis pigmentosa (xlRP) in Xp21.1 (RP3) was initially localized by deletion analysis to within a 150- to 170-kb region between the CYBB locus and the proximal deletion junction (BBJPROX) from a patient, BB, who suffered from Duchenne muscular dystrophy (DMD), McLeod syndrome, chronic granulomatous disease (CGD), and xlRP. This gene has recently been isolated and was found to be located outside and 400 kb proximal to the BB deletion. Further analysis of BBJPROX has identified the breakpoint junction sequence, showing that it occurs within an Alu repetitive element on the proximal side but with no significant homology to the distal sequence in dystrophin intron 30. Analysis of an overlapping deletion in patient NF, who suffered from DMD, CGD, and McLeod syndrome, shows that this deletion is within 4 kb but extends centromeric to BBJPROX, consistent with the location of RP3 outside the BB deletion region. A sequence with strong homology to a THE-1 transposon-like element was identified 7-13 kb from the proximal BB and NF breakpoints. These elements have been implicated in several highly unstable genomic regions. A third overlapping deletion, in a patient, SB, who suffered from CGD, McLeod syndrome, and xlRP, has here been shown to extend 380 kb proximal to the NF breakpoint, consistent with the finding that RP3 lies outside the BB deletion. This deletion has now been shown to disrupt the RP3 (RPGR) gene. The reason for the retinitis pigmentosa phenotype in patient BB remains unclear, but the most likely explanations include a long-range chromosomal position effect, a small secondary rearrangement, and the presence of a coincident autosomal form of retinitis pigmentosa.
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PMID:Analysis of three deletion breakpoints in Xp21.1 and the further localization of RP3. 892 93

McLeod syndrome is a rare X-linked disorder involving neurological defects and acanthocytosis. We examined the XK gene in three patients with neuroacanthocytosis, one of whom had cardiomyopathy, and his symptoms were very similar to those of McLeod syndrome. We found two new transversions (C to G at codon 204 and G to C at codon 205) in exon 3 in all those cases. However, the transversion at codon 205 was found in all 70 Japanese normal subjects and four non-Japanese (two Caucasian males, one Chinese female and one Micronesian female) and that at codon 204 was also detected in all 14 normal Japanese males and the four non-Japanese. These findings suggest that they are not the cause of McLeod syndrome, but normal polymorphisms which have not been reported. Moreover, there is a possibility that patients with neuroacanthocytosis similar to McLeod syndrome exist without the XK gene abnormalities.
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PMID:Analysis of the McLeod syndrome gene in three patients with neuroacanthocytosis. 926 40

Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration and unusual red-cell morphology (acanthocytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuroacanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (theta = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.
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PMID:Chorea-acanthocytosis: genetic linkage to chromosome 9q21. 938 1

The human Kx blood group antigen is carried by a 37,000 M(r) apparent molecular mass membrane polypeptide which is deficient in rare individuals with the McLeod syndrome. The X-linked human XK gene is transcribed in many tissues including adult skeletal muscle and brain, sieges of disorders observed in McLeod syndrome. We report here the cloning of the orthologous mouse XK mRNA. Comparison of XK from human and mouse revealed 80% sequence similarity at the amino acid level. The mouse XK gene is organized in two exons and is expressed in many tissues, but its expression pattern is slightly different from that of the human gene. The presence in mouse erythrocyte membrane of a 43,000 M(r) Kx-related protein was demonstrated by immunoblotting with a rabbit antiserum directed against the human protein. With non-reduced samples, a 140,000 M(r) species was detected instead of the 43,000 M(r) protein, suggesting that, as demonstrated in the Kx polypeptide might be complexed with another protein in mouse red cells, presumably the homologue of the human Kell protein of 93,000 M(r).
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PMID:Structure and expression of the mouse homologue of the XK gene. 1054 2

McLeod syndrome is a rare X-linked hematologic and neuromuscular disorder manifested by chorea, myopathy, cardiomyopathy, areflexia, hyperCKemia, and acanthocytosis. Only four mutations have been reported in the gene responsible for McLeod syndrome. We report a novel gene mutation in a Japanese family. Direct sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C-nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a 3'-frameshift. Study of family members revealed that the patient's mother was a manifesting carrier heterozygous for this mutation.
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PMID:A novel mutation of the McLeod syndrome gene in a Japanese family. 1093 May 99

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.
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PMID:McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings. 1126 14


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