Severe haemophilia A in a female resulting from an inherited gross deletion and a <i>de novo</i> codon deletion in the <i>F8</i> gene

Venceslá, Adoracioń; Fuentes‐Prior, Pablo; Baena, Manel; Quintana, Manuel; Baiget, Montserrat; Tizzano, Eduardo F.

doi:10.1111/j.1365-2516.2008.01816.x

Cited by 11 publications

(13 citation statements)

References 19 publications

(25 reference statements)

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“…Thus, female HA cases are rarely observed. However, in certain cases, there are a variety of potential genetic mechanisms leading to HA in females: i) Non-random inactivation of the normal X-chromosome in a female HA carriers (the most common cause of female HA (20,21); ii) homozygous F8 mutations (mostly reported in India where consanguineous marriages are more common) (22,23); iii) compound heterozygous mutations affecting both F8 alleles (21); and iv) X-chromosome monosomy or gross structural defects, such as a deletion or translocation (24–26). …”

Section: Discussionmentioning

confidence: 99%

Compound heterozygous hemophilia A in a female patient and the identification of a novel missense mutation, p.Met1093Ile

Qiao

Ren

et al. 2013

Molecular Medicine Reports

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Hemophilia A (HA) in females is rare. Female HA cases are often misdiagnosed as acquired HA (AHA) or as von Willebrand disease type 2N (vWD-2N). Here, we report the case of a 37-year-old female HA patient with a moderate factor VIII (FVIII) deficiency. The patient had no personal or family history of bleeding disorders, but presented with heavy uterine bleeding following surgery to remove an intrauterine device. IgG inhibitory antibodies against FVIII were undetected. A compound heterozygote mutation of the FVIII gene (F8) was found in this patient. The p.Val502Asp mutation, which has been reported previously, affects A2 domain function. A novel missense point mutation, p.Met1093Ile, was identified in the B domain. The compound heterozygote mutations in F8, p.Val502Asp and p.Met1093Ile, caused HA in this female patient, with a moderate phenotype.

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Section: Discussionmentioning

confidence: 99%

Compound heterozygous hemophilia A in a female patient and the identification of a novel missense mutation, p.Met1093Ile

Qiao

Ren

et al. 2013

Molecular Medicine Reports

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“…because of biased X-inac va on). Some of the rela vely rare cases of diseases with X-linked inheritance in women may be a ributed to compound heterozygocity for a familial muta on and a de novo muta on [1520]. One of the major causes for the increased rate of de novo muta ons on the X chromosome is that the opportuni es for pairing with the Y chromosome for the purposes of meio c crossover during prophase I of male meiosis is very limited.…”

Section: S Snegov the Experiments Of Professor Bran Ng (1977)mentioning

confidence: 99%

DNA repair systems

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The gene c bases of diseases and condi ons associated with defec ve DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensi vity syndromes. The review analyses the basic molecular mechanisms underlying the rela vely rare monogenic diseases of DNA repair and management of genome integrity as well as the common mul factorial diseases and condi ons with late onset that are associated with increased levels of oxida ve stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumula on of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous ssues. The role of major DNA damageassociated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, re noblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limi ng the presence of damaged cells and cells with poten ally oncogenic transforma on in mul cellular organisms. Special a en on is paid to ageing as a natural phenomenon and an adap ve evolu onary mechanism, with a brief outline of 'successful ageing'. The differen al rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specifici es of DNA repair profile in some types of cells (terminally differen ated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replica ve ageing and the evolu onary processes on microand macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing gene c diversity in the course of individual life and on evolu onary scale and the phenomenology of ongoing molecular evolu on are extensively reviewed. Conflict of Interests:No poten al conflict of interest was disclosed by any of the authors. Types of DNA repair systemsIf you wish for peace, prepare for war.Publius Flavius Vege us Renatus, De Re Militari (circa 380 AD).DNA damage is a very broad term, encompassing many different types of lesions in DNA.Accordingly, DNA repair comprises many different types of pathways and mechanisms covering virtually every possible type of injury to the sequence or the structure of DNA.Accep ng Lewin's defini on of DNA damage "... any change that introduces a devia on from the usual double-helical structure" [1] , we may pre...

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“…[2–4] Few other reports of homozygous female HA are mainly due to de novo mutations in one or both the X chromosomes. [56]…”

Section: Introductionmentioning

confidence: 99%

A homozygous female hemophilia A

Nair¹,

Shetty²,

Ghosh³

2012

Indian J Hum Genet

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BACKGROUND:Hemophilia A (HA), being an X-linked recessive disorder, females are rarely affected, although they can be carriers.AIMS:To study the mutation in F8 gene in an extended family with a homozygous female HA.MATERIALS AND METHODS:All the seven affected members (six males and one female) were initially screened by Conformation Sensitive Gel Electrophoresis (CSGE) and direct DNA sequencing.RESULTS:A homozygous missense mutation c.1315G>A (p.Gly420Ser) was identified in exon 9 of F8 gene in homozygous state in the affected female born of 1° consanguinous marriage and in all the affected male members of the family. Her factor VIII levels was found to be 5.5%, vWF:Ag 120%.CONCLUSION:In India, as consanguineous marriages are very common in certain communities (up to 30%), the likelihood of encountering female hemophilia is higher, although this is the first case of HA out of 1600 hemophilia families registered in our Comprehensive Haemophilia Care Center. Genetic diagnosis in such cases is not necessary as all the male children will be affected and daughters obligatory carriers.

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Severe haemophilia A in a female resulting from an inherited gross deletion and a de novo codon deletion in the F8 gene

Cited by 11 publications

References 19 publications

Compound heterozygous hemophilia A in a female patient and the identification of a novel missense mutation, p.Met1093Ile

Compound heterozygous hemophilia A in a female patient and the identification of a novel missense mutation, p.Met1093Ile

DNA repair systems

A homozygous female hemophilia A

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