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)

Aneuploidy (abnormal chromosome number) is the principal hereditary abnormality associated with either parental age or tendencies to originate in 1 parent more often than the other. Risk increases logarithmically with advancing parental age; at age 40, the risk is about 2%. In Down's syndrome, maternal age is a primary factor, but occasionally the father can be implicated. Maternal age is slightly more important than paternal age for other aneuploid syndromes. The anomalies of translocation, inversion, or deletion occur as commonly in males as females and are independent of age. They are an important factor in counseling because of their frequency and because clinically normal individuals can be carriers of genetically balanced anomalies. The risk for producing abnormal offspring can exceed 30%. A history of either several spontaneous abortions or offspring with multiple anomalies is an indication for chromosome analyses on both parents. Among known gene disorders, the severity of X-linked disorders differs in males and females. Gene mutations originate more frequently among males, and the frequency increases with advancing paternal age, particularly implicated are the Marfan syndrome, achondroplasia, hemophilia A, and the Lesch-Nyhan syndrome.
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PMID:Congenital deformities and chromosomal disorders: maternal versus paternal age. 88 78

We have described the study of a small kindred with X-linked hemophilia A. It was ascertained through a clinically affected female, the daughter of a man with moderately severe hemophilia. The pedigree and the proband's phenotype suggest that she may be a heterozygote in whom most of the normal alleles at the VIII-1 locus are not active. She has two sisters, also obligatory carriers. The three sisters exhibit the three phenotypes possible for heterozygous females: clinically affected, clinically normal but phenotypically abnormal as determined by laboratory tests, and clinically and phenotypically normal.
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PMID:The phenotypic range of hemophilia A carriers. 98 44

Classic hemophilia, (hemophilia A), is an X-linked hereditary bleeding disorder affecting half of the male offspring of female carriers. Prenatal diagnosis offers an option, namely to restrict abortions to hemophilic fetuses only, and thus retain the chance of bearing normal sons. Recently, the authors have made a prenatal diagnosis of hemophilia A in an obligate carrier with a male fetus at 24 weeks of gestation by pure fetal sampling and accurate factor VIII coagulant assay, which was repeatedly less than 1% at 28 weeks of gestation.
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PMID:A case of prenatal diagnosis of hemophilia A. 152 30

In 1989 we are continuing to move gene diagnosis over to the direct detection mode. We have sickle cell anemia, alpha-thalassemia, beta-thalassemia, Duchenne muscular dystrophy, Becker muscular dystrophy and cystic fibrosis moved to direct detection with hemophilia B and alpha-1-antitrypsin deficiency soon to be there. For indirect detection, we still have hemophilia A, and a comment on the genetics of hemophilia A is important. Remember that sickle cell anemia is caused by one mutation, while beta-thalassemia and cystic fibrosis have a finite number of alleles. Duchenne muscular dystrophy results from a different mutation for every affected individual, but most of these are deletions and can be directly detected. Hemophilia A is another X-linked disorder with almost every affected individual having a different mutation. That means that there probably are 100 ways to get beta-thalassemia and about 10,000 ways to get hemophilia A, so we need some really good novel techniques to detect these directly, and we are working hard on such techniques. I would not be surprised if hemophilia A moved into the direct detection category in the next year or so. We need to find the Huntington disease gene, and then it will move into the direct detection column. Neurofibromatosis is still in the indirect detection group but also may move very soon. Polycystic kidney disease is also still in the indirect detection column. This summarizes where prenatal and presymptomatic gene diagnosis stands in late 1989.
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PMID:Current status of prenatal diagnosis by DNA analysis. 209 48

Most structural congenital heart defects (CHD) are thought to be multifactorially determined, but the precise causal factors usually are unknown. One may postulate that vascular events, such as hemorrhage in the developing embryo, could influence morphogenesis of the heart. One method of studying this hypothesis is to determine the frequency of CHD in persons with heritable bleeding diatheses and their families. We reviewed retrospectively medical and family histories of 120 hemophilia A and 14 hemophilia B patients seen in our Genetics Department. The family histories included 1,126 maternal relatives of hemophiliac patients. We also reviewed the family histories of 138 patients with X-linked disorders who did not have bleeding diatheses or syndromes associated with CHD; these histories included 960 maternal relatives. There was one confirmed case of a CHD in 134 hemophilia patients, giving a frequency of 0.75% compared to 0.8% in the general population at birth. There was no apparent difference in the frequency of CHD in hemophilia A and B patients compared to the general population or in the relatives of hemophilia patients as compared to control individuals.
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PMID:Frequency of congenital heart defects in patients with hemophilia. 236 33

Hemophilia A is an X-linked bleeding disorder caused by a deficiency or abnormality of factor VIII, affecting approximately 1 male in 10,000. A subgroup of the patients develops inhibitors against factor VIII during substitution therapy. Because a considerable percentage of all cases is thought to result from de novo mutations, it is likely that many different molecular lesions lead to hemophilia A. In order to understand the molecular basis of this disorder, we examined 160 patients with different clinical features using factor VIII gene probes. We could identify six different deletions and seven nonsense mutations within the factor VIII gene. Family analysis revealed that five of these mutations occurred de novo within two generations; two of them arose in the maternal grandfather and three in the mother. In one of these mothers we could identify a mitotic origin. Mapping of the deletions showed no deletion-prone region within the gene. Furthermore, we could not find any correlation between the particular gene defects and "inhibitor" phenotypes.
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PMID:Molecular defects in hemophilia A: identification and characterization of mutations in the factor VIII gene and family analysis. 247 10

Hemophilia A is an X-linked bleeding disorder resulting from a defect in coagulation factor VIII. Clinical severity, the level of factor VIII activity and coagulant antigen vary widely. However, the three parameters breed true in families, indicating that the phenotypic expression directly reflects the genetic defect. In about 5%, hemophilia A results from partial deletion of the factor VIII gene and is clinically severe. In another 5% single base mutations have been found, which destroy the binding sites for the restriction enzyme TaqI. They can be "nonsense" mutations resulting in stop codons and clinically severe hemophilia, or "missense" mutations resulting in amino acid changes and milder forms of hemophilia. By the use of the polymerase chain reaction and denaturing gradient gel electrophoresis we have detected several point mutations. The formation of anti-factor VIII antibodies appears to be more frequent in patients with defects resulting in absence of factor VIII protein. Carrier detection and prenatal diagnosis can be made with 100% certainty in families with identified mutations. In their absence, polymorphisms affecting recognition sequences for 2 restriction enzymes (BclI and XbaI) within or outside the factor VIII gene can serve as a tag for the mutation and be followed through the pedigree. In the absence of any informative polymorphism the conventional methods for carrier detection are still helpful.--In roughly 1/3 of the patients, the mutation appears "sporadic". However, it can usually be traced within one or two generations of the proband. --Some patients have mosaicism for sporadic mutations, indicating that mutagenesis not necessarily occurs at the level of the gametes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular genetics of hemophilia A. 250 18

Hemophilia A is an X-linked disease of coagulation caused by deficiency of factor VIII. Using cloned cDNA and synthetic oligonucleotide probes, we have now screened 240 patients and found CG-to-TG transitions in an exon in nine. We have previously reported four of these patients; and here we report the remaining five, all of whom were severely affected. In one patient a TaqI site was lost in exon 23, and in the other four it was lost in exon 24. The novel exon 23 mutation is a CG-to-TG substitution at the codon for amino acid residue 2166, producing a nonsense codon in place of the normal codon for arginine. Similarly, the exon 24 mutations are also generated by CG-to-TG transitions, either on the sense strand producing nonsense mutations or on the antisense strand producing missense mutations (Arg to Gln) at position 2228. The novel missense mutations are the first such mutations observed in association with severe hemophilia A. These results provide further evidence that recurrent mutations are not uncommon in hemophilia A, and they also allow us to estimate that the extent of hypermutability of CG dinucleotides is 10-20 times greater than the average mutation rate for hemophilia A.
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PMID:Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides. 283 55

The diversity of hereditary pathology in 5 regions of Kostroma district was studied. 32 nosological forms of autosomal dominant, 30 autosomal recessive and 7 X-linked recessive disorders were found. The most frequent autosomal dominant disorders were: neurofibromatosis, pigmentary degeneration of retina, hypochondroplasia, ichtiosis, idiopathic scoliosis. The most frequent among the autosomal recessive disorders were: oligophrenia, pigmentary degeneration of retina, muscular atrophy of juvenile Kugelberg--Welander type, congenital cataract. The most frequent X-linked disorders were: muscular Duchenne type dystrophy and hemophilia A. Analysis of mutant gene distribution over the territory by the study of birthplaces of probands and their parents was carried out.
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PMID:[Medical genetics study of the population of Kostroma Province. II. The diversity of hereditary pathology in 5 districts of the province]. 293 68

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, we have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes.
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PMID:Characterization of five partial deletions of the factor VIII gene. 303 54


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