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Identification of novel compound heterozygous variants in a pedigree affected with hereditary coagulation factor XI deficiency / 中华医学遗传学杂志
Chinese Journal of Medical Genetics ; (6): 501-504, 2020.
Article in Chinese | WPRIM | ID: wpr-826547
ABSTRACT
OBJECTIVE@#To analyze the phenotype and genetic basis for a pedigree affected with hereditary coagulation factor XI deficiency.@*METHODS@#Activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (FIB), FXI activity (FXIC) and the antigen of FXI (FXIAg) were determined for the proband and members from his pedigree. Sanger sequencing was used to analyze all exons, exon-intronic boundaries, as well as the 5'- and 3'- untranslated regions of the F11 gene. Suspected variants were verified in her family members and confirmed by reverse sequencing. The impact of the variants on the protein function was predicted by using PolyPhen-2 and SIFT software. The protein structure and amino acid interaction were analyzed by using Swiss-PdbViewer.@*RESULTS@#The APTT, FXIC and FXIAg of the proband and her sister were significantly reduced to 73.0 s, 10.0%, 15.0% and 87.1 s, 2.0% and 11.5%, respectively. APTT of some family members was slightly prolonged, and FXIC and FXIAg also decreased to various extents. DNA sequencing revealed that the proband and her sister have carried compound heterozygous variants of c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) respectively in exons 7 and 9 of the F11 gene. Her father, sister and daughter were heterozygous for the c.738G>A (p.Trp228stop) variant, while her mother and nephew were heterozygous for the c.938G>T (p.Ser295Ile). Both PolyPhen-2 and SIFT predicted that the p.Ser295Ile variant is likely to be deleterious and can affect the protein function. Modeling analysis indicated that the p.Ser295Ile variant may lead to disruption of a hydrogen bond, resulting in alteration of protein structure and instability.@*CONCLUSION@#The compound heterozygous c.738G>A (p.Trp228stop) and c.938G>T (p.Ser295Ile) variants of the F11 gene probably underlie the decreased FXI level in this pedigree.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pedigree / Genetic Variation / Factor XI Deficiency / Genetics / Heterozygote / Mutation Type of study: Prognostic study Limits: Female / Humans Language: Chinese Journal: Chinese Journal of Medical Genetics Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pedigree / Genetic Variation / Factor XI Deficiency / Genetics / Heterozygote / Mutation Type of study: Prognostic study Limits: Female / Humans Language: Chinese Journal: Chinese Journal of Medical Genetics Year: 2020 Type: Article