Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency

Autor: Jean-Luc Pellequer, Jean-François Schved, Tahir Shamsi, P. Aguilar-Martinez, Munira Borhany, Muriel Giansily-Blaizot, Grégory Moulis, H. Boijout
Přispěvatelé: Department of Haematology, Haemostasis & Thrombosis, National Institute of Blood Disease & Bone Marrow Transplantation, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biochimie et Toxicologie Nucléaire (SBTN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2013
Předmět:
Male
Factor VII Deficiency
030204 cardiovascular system & hematology
Gene mutation
medicine.disease_cause
MESH: Genotype
Exon
chemistry.chemical_compound
0302 clinical medicine
Genotype-phenotype distinction
phenotype-genotype relationship
MESH: Child
Medicine
Missense mutation
Pakistan
Child
Promoter Regions
Genetic
Genetics (clinical)
Genetics
0303 health sciences
Mutation
MESH: Asian Continental Ancestry Group
Factor VII
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Homozygote
Hematology
General Medicine
3. Good health
Phenotype
Hepatocyte Nuclear Factor 4
MESH: Young Adult
Child
Preschool
Female
MESH: Hepatocyte Nuclear Factor 4
MESH: Pakistan
MESH: Factor VII
MESH: Homozygote
Protein Binding
Adolescent
Genotype
Mutation
Missense
Consanguinity
MESH: Phenotype
03 medical and health sciences
Young Adult
Asian People
MESH: Promoter Regions
Genetic
MESH: Protein Binding
Humans
FVII deficiency
Gene
rare bleeding disorder
Alleles
030304 developmental biology
MESH: Adolescent
MESH: Mutation
Missense
MESH: Humans
Binding Sites
business.industry
MESH: Alleles
MESH: Child
Preschool
MESH: Male
chemistry
MESH: Binding Sites
MESH: Factor VII Deficiency
mutation
business
MESH: Female
Zdroj: Haemophilia
Haemophilia, 2013, 19 (6), pp.893-897. ⟨10.1111/hae.12186⟩
Haemophilia, Wiley, 2013, 19 (6), pp.893-897. ⟨10.1111/hae.12186⟩
ISSN: 1365-2516
1351-8216
DOI: 10.1111/hae.12186⟩
Popis: International audience; Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series.
Databáze: OpenAIRE
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