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[Phenotype and genotype analyses of two pedigrees with inherited fibrinogen deficiency].
Jia, K Q; Su, Z X; Chen, H L; Zheng, X Y; Zeng, M L; Zhang, K; Ye, L Y; Yang, L L; Jin, Y H; Wang, M S.
Afiliación
  • Jia KQ; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Su ZX; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Chen HL; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Zheng XY; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Zeng ML; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Zhang K; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Ye LY; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Yang LL; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Jin YH; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
  • Wang MS; Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
Zhonghua Xue Ye Xue Za Zhi ; 44(11): 930-935, 2023 Nov 14.
Article en Zh | MEDLINE | ID: mdl-38185523
ABSTRACT

Objective:

To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis.

Methods:

The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (FgAg) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation.

Results:

The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BßAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BßSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BßAla98Asp and p.BßSer473* were pathogenic. Protein models demonstrated that the p.BßAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BßSer473* mutation resulted in protein truncation.

Conclusion:

The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BßAla98Asp heterozygous missense mutation and the p.BßSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Afibrinogenemia Tipo de estudio: Prognostic_studies Límite: Humans Idioma: Zh Revista: Zhonghua Xue Ye Xue Za Zhi Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Afibrinogenemia Tipo de estudio: Prognostic_studies Límite: Humans Idioma: Zh Revista: Zhonghua Xue Ye Xue Za Zhi Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: China