Molecular study of VWF gene from Mexican Mestizo patients with von Willebrand disease, and the finding of three new mutations

Melo-Nava, Brenda; Benítez, Herminia; Palacios, JL; Nieva, Beatriz; Arenas, Diego; Jaloma‐Cruz, Ana Rebeca; Navarrete, Carmen; Salamanca, F; Peñaloza, Rosenda

doi:10.1016/j.bcmd.2007.06.007

Cited by 7 publications

(7 citation statements)

References 15 publications

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“…4 A small number of mutations outside of exon 28 are listed, and these include p.C1196R encoded by exon 27, which is within the region of type 2A(IIE) mutations reported by Schneppenheim et al 9 Three mutations in exons 30 to 31 encoding the A3 domain are listed as type 2M, and these result in reduced binding to collagen 13,14 while a single mutation is reported to result in 2M VWD in exon 52 (p.P2781S), but collagen-binding analysis is not reported. 15 A further mutation in the A3 domain that affects collagen binding and could be considered as a 2M mutation (p.S1731T) was submitted under the ''Unclassified'' category. 16 The A3 domain mutations span amino acids (AAs) 1731 to 1786.…”

Section: Type 2mmentioning

confidence: 99%

The International Society on Thrombosis and Haematosis von Willebrand Disease Database: An Update

Hampshire¹,

Goodeve²

2011

Semin Thromb Hemost

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The online locus-specific database for von Willebrand disease (VWFdb) acts as a repository for sequence variant data and associated resources for those with an interest in the disorder. It currently holds details of 561 mutations and 217 polymorphisms in the von Willebrand factor (VWF) gene. Lists can be queried and displayed by VWF region or disease type. A total of 42% of the mutations are located in the large exon 28, the most heavily studied VWF region, and mutations have been reported in all but 4 of the 51 protein-coding exons. Polymorphisms are reported in the 5' and 3' untranslated regions and in 33 exons and 35 introns. Additional resources include references linked to sequence variation entries, descriptors of each VWD type, genomic and cDNA sequences, nomenclature for VWF and its attributes, Human Genome Variation Society sequence variant nomenclature recommendations, multimer images, and related densitometry traces for type 2 VWD. Analysis of recessively inherited VWD indicates that whereas the majority (69%) of type 3 VWD patients are homozygous for their mutations, the majority (62%) of 2N patients are compound heterozygous. Comparison of missense substitutions reported as mutations with those reported as polymorphisms suggests that loss or gain of cysteine, tryptophan, methionine, or glutamate residues are more likely to result in a pathogenic effect than loss/gain of other VWF residues.

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Section: Type 2mmentioning

confidence: 99%

The International Society on Thrombosis and Haematosis von Willebrand Disease Database: An Update

Hampshire¹,

Goodeve²

2011

Semin Thromb Hemost

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“…Previous studies on VWD in the Mexican population have also genetically sequenced their patients 13 to differentiate between VWD and haemophilia A 14 or to address other confounding clinical and laboratory issues of VWD diagnosis 11,12 …”

Section: Discussionmentioning

confidence: 99%

“…8,11,12 The supplemental discriminatory tests required to distinguish types 2M, 2N, and 1C VWD, as well as genetic variant identification and genotypephenotype correlation analyses, are not routine for VWD. In Mexico, Sanger sequencing has revealed inherited pathogenic variants in exon 28 of the VWF gene 13 and the VWF:FVIIIB assay is used to discriminate between type 2N VWD and haemophilia 14 ; however, these analyses are rare. Therefore, this research aimed to characterise the type and subtype of VWD in a cohort of patients from Western Mexico with a history of abnormal bleeding and suspicion of VWD.…”

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confidence: 99%

Diagnosis of von Willebrand disease in Western Mexico

et al. 2020

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Introduction Von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 0.1%, characterised by quantitative or functional deficiency of von Willebrand factor (VWF). VWD diagnosis is based on symptomology, biochemical and genetic tests, but limited laboratory resources and VWD heterogeneity still generate an important subdiagnosis gap worldwide and in our country. Aim To identify the type and subtype of VWD in a cohort of patients with a history of excessive bleeding in Western Mexico. Methods This prospective cohort study from 2012 to 2019 included patients with mucocutaneous bleeding or abnormal laboratory tests. A standardised questionnaire and confirmatory tests were applied: FVIII:C, VWF activity, VWF antigen, and VWF multimeric analysis. Results Of the 297 patients recruited, 207 (69.7%) were excluded because their values exceeded 50% in VWF activity and VWF antigen. Of those 90 remaining, 54 (18.2%) had low VWF, and only 36 patients (12.1%) were diagnosed with VWD. Among them, 17 (47.2%) had quantitative deficiencies, of whom 14 were assigned as type 1 and 3 as type 3.The remaining 19 cases were diagnosed as type 2 (52.8%): type 2A and 2B were the most frequent with 6 and 7 cases respectively; 4 cases were possible type 2M and two suggestive of 2N, however, this was not confirmed. Conclusion This study highlights the challenges of VWD diagnosis using a comprehensive panel of diagnostic tests which should extend to supplemental tests of VWF:CB, VWF:FVIIIB, and sequencing the VWD gene to confirm the results from the panel assays.

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“…1), como la variante «Vicenza» (c.3614G>A) en el exón 27, que provoca un cambio de una arginina por una histidina en la posición 1205 del VWF y con ello disminuye el tiempo en que el VWF permanece en el plasma; esta mutación es una de las más estudiadas y se relaciona con la enfermedad de von Willebrand tipo 1 40,41 . Incluso existe un estudio molecular del gen VWF en pacientes mestizos mexicanos, en el que se describen 3 nuevas mutaciones: E1447Q en un paciente con la enfermedad de von Willebrand tipo 1 y diabetes; P2781S en un paciente con tipo 2M; y P812L en otro paciente tipo 1/2N 22,42 . Este alto grado de polimorfismos en el VWF, junto con el gran tamaño del gen y la presencia de un seudogén parcial, hacen que la secuenciación completa del gen y la interpretación de datos sean difíciles y complejas.…”

Section: Variaciones Y Mutaciones En El Factor De Von Willebrandunclassified

Enfermedad de von Willebrand, biología molecular y diagnóstico

Hernández-Zamora

Zavala-Hernández

Quintana-González

et al. 2015

Cirugía y Cirujanos

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Von Willebrand disease is highly heterogeneous due to the molecular mechanisms that produce the various clinical and laboratory phenotypes. In Mexico there are few studies related to this disease; therefore it is essential to conduct a comprehensive study including clinical, basic, and special testing laboratory tests, in order to establish a correct diagnosis, develop new therapeutic approaches, and offer the appropriate medical care and genetic counselling.

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Molecular study of VWF gene from Mexican Mestizo patients with von Willebrand disease, and the finding of three new mutations

Cited by 7 publications

References 15 publications

The International Society on Thrombosis and Haematosis von Willebrand Disease Database: An Update

The International Society on Thrombosis and Haematosis von Willebrand Disease Database: An Update

Diagnosis of von Willebrand disease in Western Mexico

Enfermedad de von Willebrand, biología molecular y diagnóstico

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