Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0684275 (haemophilia)
 10,958 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemophilia is caused by wide spectrum of different mutations in the F8C gene which made the direct DNA diagnosis of the diseases not the case of choice. Indirect DNA diagnosis by means of linked restriction fragment length polymorphisms (RFLPs) provides the alternative. Using this method authors identified de novo mutation in a family requiring prenatal diagnosis of hemophilia A. This de novo mutation arose during the spermatogenesis of the proband's father. Attempts to characterize the mutation on the molecular level are presented. (Ref. 15, Fig. 1.).
 ...
PMID:[Identification of a de novo mutation in a factor FVIII:C gene in a family requesting prenatal diagnosis of hemophilia A]. 136 17

Two novel restriction fragment length polymorphisms (RFLPs) around the DXS115 (767) locus, detectable with the restriction enzymes MspI, are described. Since DXS115 is closely linked to the factor VIII gene (F8C), the MspI RFLP was employed in haemophilia A carrier detection. The utility of these RFLPs lies in the increased applicability and accuracy of diagnoses carried out in cases where available intragenic markers are uninformative.
 ...
PMID:Improved carrier detection of haemophilia A using novel RFLPs at the DXS115 (767) locus. 169 59

In a family with a single case of hemophilia A genetic counselling was requested by the pregnant aunt of the propositus. The haplotypes generated by two extra-genic RFLPs, at DXS52 (St14/Taq1) and DXS15 (DX13/BglII), and one intragenic RFLP in F8C (647/BclI) indicated that: she was not a carrier; the case of hemophilia resulted from a de novo mutation in a grandfather's gamete.
 ...
PMID:De novo mutation in hemophilia A established by DNA haplotype analysis and precluding prenatal diagnosis. 287 41

Genetic transmission in manic depressive illness (MDI) has been explored in twins, adoption, association, and linkage studies. The X-linked transmission hypothesis has been tested by using several markers on chromosome X: Xg blood group, colour blindness, glucose-6-phosphate dehydrogenase (G6PD), factor IX (haemophilia B), and DNA probes such as DXS15, DXS52, F8C, ST14. The hypothesis of autosomal transmission has been tested by association studies with the O blood group located on chromosome 9, as well as linkage studies on chromosome 6 with the Human Leucocyte Antigens (HLA) haplotypes and on Chromosome 11 with DNA markers for the following genes: D2 dopamine receptor, tyrosinase, C-Harvey-Ras-A (HRAS) oncogene, insuline (ins), and tyrosine hydroxylase (TH). Although linkage studies support the hypothesis of a major locus for the transmission of MDI in the Xq27-28 region, several factors are limiting the results, and are discussed in the present review.
 ...
PMID:Minireview: Molecular genetics in affective illness. 842 7

Preimplantation genetic diagnosis (PGD) first consisted of the selection of female embryos for patients at risk of transmitting X-linked recessive diseases. Advances in molecular biology now allow the specific diagnosis of almost any Mendelian disease. For families with an identified X-linked recessive disease-causing mutation, non-specific diagnosis by sex identification can be considered as a sub-standard method, since it involves the unnecessary disposal of healthy male embryos and reduces success rate by diminishing the pool of embryos eligible for transfer. The most telomeric part of the X-chromosome long arm is a highly gene-rich region encompassing disease genes such as haemophilia A, X-linked adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti. We developed five single-cell triplex amplification protocols with microsatellite markers DXS1073, DXS9901 (BGN), G6PD, DXS1108, DXS8087 and F8C-IVS13 located in this Xq terminal region. These tests allow the diagnosis of all diseases previously mentioned providing that the genetic material allowing the identification of the morbid allele can be obtained. The choice of the microsatellite set to use depends on the localisation of the gene responsible for the diagnosed pathology and on the informativity of the markers in particular families. Single-cell amplification efficiency was assessed on single lymphocytes. Amplification rate of the different markers ranged from 89-97% with an allele drop out rate of 2-19%. So far PGD has been carried out for three carrier females at risk of transmitting X-linked adrenoleukodystrophy, X-linked hydrocephalus and hemophilia A. The latter one is now pregnant.
 ...
PMID:Single cell co-amplification of polymorphic markers for the indirect preimplantation genetic diagnosis of hemophilia A, X-linked adrenoleukodystrophy, X-linked hydrocephalus and incontinentia pigmenti loci on Xq28. 1467 43

Haemophilia A is the most common inherited bleeding disorder caused by defects in the F8C gene that encodes coagulation factor VIII. This X-linked recessive disorder occurs in approximately 1:5000 males. Haemophilia A is diagnosed based on normal prothrombin time, altered activated partial thromboplastin time and reduced factor VIII activity in plasma. Carrier females are usually asymptomatic and can be identified only by molecular analysis. The most frequent mutations in F8C are intron 22 and 1 inversions, which occur in approximately 50% and 5% of patients, respectively, with a severe phenotype. Large gene deletions are observed in approximately 5% of alleles from patients with severe haemophilia A. The remaining severe cases and all moderate and mild cases result from numerous point mutations and small insertions/deletions, which are de novo mutations in one-third of cases. Thus, molecular diagnosis of carrier status and prenatal diagnosis in families without intron 22 or 1 inversions is based on scanning techniques or gene sequencing. When the disease-causing mutation cannot be identified, molecular diagnosis is performed by linkage analysis of several DNA polymorphic markers linked to F8C. Given the clinical heterogeneity among haemophilic patients, many groups, including our own, have examined the relationships between prothrombotic gene variants and haemophilic phenotype to investigate whether prothrombotic gene variants modify clinical expression of the disease.
 ...
PMID:Haemophilia A: molecular insights. 1743 20

Haemophilia A (HA) and haemophilia B (HB) are the most common X-linked inherited bleeding disorders. It is important to detect the carrier women in families with HA/HB and subsequent antenatal diagnosis of confirmed carriers. This study consists of 102 HA families which include 68 mothers for prenatal diagnosis and 107 female relatives for carrier diagnosis, and 29 HB families which include 16 mothers and 31 female relatives respectively. The rapid fluorescent PCR with two groups of different combined polymorphism markers was applied for linkage analysis in HA and HB families respectively. The Amelogenin gene was added to help the detection of gender diagnosis. Gene sequencing was also used to detect the mutations directly. There were 37 causative F8C mutations (23 novel) and 24 causative F9C mutations (eight novel) found in this cohort of patients. Few of the women could not be diagnosed due to homologous recombination and/or inability to locate the mutation. Complicated cases have been found in some families. With regard to carrier and prenatal diagnosis, it was considered that genetic diagnosis by linkage analysis and direct sequencing was successful. Some special families might require combination of the linkage analysis and gene sequence for a successful diagnosis. New intragenic SNP and STR sites special to Chinese population need to be discovered.
Haemophilia 2012 Mar
PMID:The status of carrier and prenatal diagnosis of haemophilia in China. 2191 Jul 85