Haemophilia A and cardiovascular morbidity in a female SHAM syndrome carrier due to skewed X chromosome inactivation

Janczar, Szymon; Kosińska, Joanna; Płoski, Rafał; Pastorczak, Agata; Wegner, Olga; Zalewska-Szewczyk, Beata; Paige, Adam J.W.; Borowiec, Maciej; Młynarski, Wojciech

doi:10.1016/j.ejmg.2015.12.004

Cited by 12 publications

(17 citation statements)

References 12 publications

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“…Moreover, his maternal uncle (severe HA with inhibitor) also died after haemorrhagic stroke. Finally, Janczar et al . recently reported that female carriers of a large deletion including F8 and BRCC3 could have a variable clinical presentation of moyamoya syndrome attributed to the random X‐chromosome inactivation level.…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of five F8 complex rearrangements: utility for haemophilia A genetic counselling

et al. 2017

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Because several F8 neighbouring genes are associated with other pathologies such as XLID and cardiovascular disease, all HA patients where complex Xq28 rearrangement was suspected should be referred to a geneticist for possible utility of a pangenomic study. Such investigation should be carefully considered in genetic counselling in female carriers to assess the risk of transmitting severe HA with a "contiguous gene syndrome".

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Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of five F8 complex rearrangements: utility for haemophilia A genetic counselling

et al. 2017

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“…The description of severe haemophilia B in women is restricted to very few cases worldwide. 6,7 We initiated a nationwide survey for genetic causes of severe/moderate female haemophilia B to assess the prevalence of the disorder and potentially uncover novel disease-associated genomic alterations. 4,5 While we believe that every patient with ultra rare disease deserves thorough genetic diagnostics, the results of which may guide treatment and enable genetic counselling, genetic testing in the setting of haemophilia is not routine in Poland.…”

mentioning

confidence: 99%

“…Furthermore, exceedingly rare disorders or surprising comorbidities justify thorough genetic diagnostics as they might be caused by complex genomic events disrupting several genes, similar to a contiguous gene syndrome associated with haemophilia A that we previously described. 6,7 We initiated a nationwide survey for genetic causes of severe/moderate female haemophilia B to assess the prevalence of the disorder and potentially uncover novel disease-associated genomic alterations. Prior to this study, we were not aware of any reports on molecular causes of this ultrarare disease in Poland.…”

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confidence: 99%

Puzzling outcome of the nationwide genetic survey of severe/moderate female haemophilia B in Poland

et al. 2019

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“…In this specific CGS, the phenotype includes severe HA, moyamoya angiopathy, dysmorphia and hypertension. In carriers of such deletion, clinical symptoms will depend on their X chromosome inactivation pattern . The number of patients with severe HA and BRCC3 deletion is presently unknown because the telomeric part of F8 is rarely subject to genetic analysis when a deletion including exon 1 is detected.…”

Section: Contiguous Gene Syndrome In Hemophilia Patientsmentioning

confidence: 99%

“…In carriers of such deletion, clinical symptoms will depend on their X chromosome inactivation pattern. 55 The number of patients with severe HA and BRCC3 deletion is presently unknown because the telomeric part of F8 is rarely subject to genetic analysis when a deletion including exon 1 is detected. One should be aware that some patients with HA may be affected by moyamoya angiopathy and in this case they are at risk of ischemic stroke.…”

Section: Conti G Uous G Ene Syndrome In Hemophilia Patientsmentioning

confidence: 99%

Review of molecular mechanisms at distal Xq28 leading to balanced or unbalanced genomic rearrangements and their phenotypic impacts on hemophilia

Lannoy

Hermans

2018

Haemophilia

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The distal Xq28 region is very gene-rich, comprising a relatively large number of low-copy repeats (LCRs) predisposing to genomic rearrangements. The best-known rearrangement at this locus is the F8 intron 22 inversion, responsible for up to 45% of severe hemophilia A (HA) cases. An additional inversion of intron 1 of F8 has more recently been described, affecting 2%-5% of patients with severe HA. These "balanced" rearrangements are mediated by intrachromosomal homologous recombination between inversely oriented LCRs located in intron 1 or 22 and other extragenic copies positioned more telomerically outside the F8 gene. The successive innovations of semi-quantitative technologies like multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH) have rendered it possible to highlight a significant number of "unbalanced" rearrangements associated or not with these inversions. Some rearrangements are generated by the non-allelic homologous recombination (NAHR) pathway between directly oriented LCRs. Others are probably the result of unequal crossing-over or U-loop exchanges during female meiosis. This review sought to provide an overview of the mechanisms underlying rearrangements at the distal Xq28 locus and discuss their clinical impacts other than HA, such as risks of developing high inhibitor levels and spontaneous abortion, as well as other pathologies like cardiovascular disease or potentially X-linked intellectual disease.

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Haemophilia A and cardiovascular morbidity in a female SHAM syndrome carrier due to skewed X chromosome inactivation

Cited by 12 publications

References 12 publications

Molecular cytogenetic characterization of five F8 complex rearrangements: utility for haemophilia A genetic counselling

Molecular cytogenetic characterization of five F8 complex rearrangements: utility for haemophilia A genetic counselling

Puzzling outcome of the nationwide genetic survey of severe/moderate female haemophilia B in Poland

Review of molecular mechanisms at distal Xq28 leading to balanced or unbalanced genomic rearrangements and their phenotypic impacts on hemophilia

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