Genetic analysis and clinical features of a pedigree affected with hereditary coagulation factor Ⅶ deficiency caused by compound heterozygotic mutations / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
;
(6): 1006-1009, 2019.
Artículo
en Chino
| WPRIM
| ID: wpr-776756
ABSTRACT
OBJECTIVE@#To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis.@*METHODS@#The FⅦ antigen (FⅦAg) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦC) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank.@*RESULTS@#The propositus had prolonged PT (36.3 s), with FⅦC and FⅦAg significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦC (86%-120%). The FⅦAg of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein.@*CONCLUSION@#The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Linaje
/
Factor VII
/
Pruebas Genéticas
/
Deficiencia del Factor VII
/
Genética
/
Heterocigoto
/
Mutación
Tipo de estudio:
Estudio pronóstico
Límite:
Femenino
/
Humanos
/
Masculino
Idioma:
Chino
Revista:
Chinese Journal of Medical Genetics
Año:
2019
Tipo del documento:
Artículo
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