Type I mutation in the F11 gene is a third ancestral mutation which causes factor XI deficiency in Ashkenazi Jews

Peretz, Hava; Salomon, Ophira; Mor‐Cohen, Ronit; Usher, Sali; Zucker, Michal; Zivelin, Ariella; Seligsohn, Uri

doi:10.1111/jth.12137

Cited by 9 publications

(8 citation statements)

References 32 publications

(42 reference statements)

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“…The c.1716+1G>A variant in the F11 gene causing Factor XI deficiency is considered to be an AJ mutation. 22 Two galactosemia variants in the GALT gene were added, Q188R and K285N, due to their high frequency in Eastern European populations. 23 The E372X variant in the BCKDHB gene, which causes Maple Syrup Urine disease, was also added due to its high frequency in the AJ population.…”

Section: Resultsmentioning

confidence: 99%

Expanded genetic screening panel for the Ashkenazi Jewish population

Baskovich

Hiraki

Upadhyay

et al. 2016

Genetics in Medicine

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Purpose Carrier screening programs that identify the presence of known mutations have been effective for reducing the incidence of autosomal recessive conditions in the Ashkenazi Jewish population and other populations. Yet, these programs have not realized their full potential. Furthermore, many known autosomal recessive and dominant conditions are not screened for and the molecular basis of other conditions for which screening might be offered is unknown. Methods Through literature review and annotation of full sequenced genomes from healthy individuals, we expanded the list of mutations. Mutations were identified in a sample of 128 fully sequenced Ashkenazi Jewish genomes that were filtered through clinical databases and curated manually for clinical validity and utility using the American College of Medical Genetics scoring (ACMG) system. Other known mutations were identified through literature review. Results A panel of 203 mutations was identified for 92 autosomal recessive, 24 autosomal dominant, and 4 X-linked disorders. Conclusion Screening for a broader range of disorders could not only further reduce the incidence of autosomal recessive disorders, but could also offer the benefits of early or presymptomatic diagnosis.

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Section: Resultsmentioning

confidence: 99%

Expanded genetic screening panel for the Ashkenazi Jewish population

Baskovich

Hiraki

Upadhyay

et al. 2016

Genetics in Medicine

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“…38 Recently, a founder effect was also clearly established for the type I mutation (c.1716 þ 1G > A) by analyzing 13 unrelated families harboring this genetic defect. 85 In patients belonging to different ethnic groups, a significantly higher level of allelic heterogeneity has been reported. Remarkable exceptions are represented by some "closed populations" harboring mutations compatible with a founder effect: Cys38Arg in French Basques, 39 Gln88Stop in French families from Nantes, 18 Cys128Stop in Britons, 38 Ile436Lys in Northeastern Italy, 86 and Q263X in Korean patients.…”

Section: Founder Mutationsmentioning

confidence: 99%

Congenital Factor XI Deficiency: An Update

Duga

Salomon

2013

Semin Thromb Hemost

157

192

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Severe factor XI (FXI) deficiency is an injury-related bleeding disorder, common in Ashkenazi Jews (with two mutations prevailing), but rare worldwide (with heterogeneous mutations). In the past two decades, more than 220 mutations in the FXI gene have been reported in patients with FXI deficiency, of which 7 showed a founder effect. Inhibitors to FXI were described in patients with null-allele mutations, following exposure to plasma, FXI concentrates, or anti-RhD immunoglobulin. Treatment of patients with severe FXI deficiency remains challenging because factors influencing bleeding risks are still unknown. The use of lower doses of recombinant activated factor VII in comparison with the doses commonly applied in hemophilia A or B seems promising also when assessed in vitro by thrombin generation test. Recently, FXI has been shown to have a separate role in hemostasis and in thrombosis. In animal models, targeting FXI by knocking out the gene or by using FXI-neutralizing antibodies, antisense oligonucleotides, and peptidomimetic inhibitors, prevents arterial and vein thrombosis. The homology between human and murine FXI and the significant antithrombotic effect of FXI deficiency in animal models resulted in the development of a novel approach of targeting FXI for prevention of thrombosis without impairing hemostasis in high-risk patients. The acceptance of FXI as a risk factor for thrombosis is a new concept, and patients with severe FXI deficiency might gain profit during life course.

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“…Text books of medicine still reflect a low prevalence for FXI deficiency (1/10 000‐50 000) and restrict to specific populations a high incidence of FXI deficiency. Development of whole communities from relatively few individuals due to extreme genetic drifts caused by drastic changes in population size, migration and founder effects sustain the high frequency of FXI deficiency in these ethnic groups . However, increasing evidences from epidemiological studies performed in different European and Asian countries suggest that this disorder might have higher incidence than originally believed .…”

Section: Discussionmentioning

confidence: 98%

“…Text books of medicine still reflect a low prevalence for FXI deficiency (1/10 000-50 000) and restrict to specific populations a high inci- groups. 4,26 However, increasing evidences from epidemiological studies performed in different European and Asian countries suggest that this disorder might have higher incidence than originally believed. 5,7,9,11,13 A recent study that explored publicly available exome-based data obtained from >60 000 individuals belonging to different ethnicities found a prevalence of F11 pathogenic 27 The recurrent mutations identified in this study might be specific of Caucasians.…”

Section: Discussionmentioning

confidence: 99%