Congenital fibrinogen disorders—Strengthening genotype–phenotype correlations through novel genetic diagnostic tools

Radha Ramanan; James D. McFadyen; Andrew C. Perkins; Huyen A. Tran

doi:10.1111/bjh.19039

Congenital fibrinogen disorders—Strengthening genotype–phenotype correlations through novel genetic diagnostic tools

Radha Ramanan, James D. McFadyen, Andrew C. Perkins, Huyen A. Tran

Australian Centre for Blood Diseases

Research output: Contribution to journal › Review Article › Research › peer-review

11 Citations (Scopus)

Abstract

Congenital fibrinogen disorders or CFDs are heterogenous, both in clinical manifestation and array of culprit molecular lesions. Correlations between phenotype and genotype remain poorly defined. This review examines the genetic landscape discovered to date for this rare condition. The question of a possible oligogenic model of inheritance influencing phenotypic heterogeneity is raised, with discussion of the benefits and challenges of sequencing technology used to enhance discovery in this space. Considerable work lies ahead in order to achieve diagnostic and prognostic precision and subsequently provide targeted management to this complex cohort of patients.

Original language	English
Pages (from-to)	355-368
Number of pages	14
Journal	British Journal of Haematology
Volume	203
Issue number	3
DOIs	https://doi.org/10.1111/bjh.19039
Publication status	Published - Nov 2023

Keywords

afibrinogenemia
congenital fibrinogen disorders
dysfibrinogenemia
genotype-phenotype correlation
hypodysfibrinogenemia
hypofibrinogenemia
nex-generation sequencing

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10.1111/bjh.19039Licence: CC BY-NC-ND

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title = "Congenital fibrinogen disorders—Strengthening genotype–phenotype correlations through novel genetic diagnostic tools",

abstract = "Congenital fibrinogen disorders or CFDs are heterogenous, both in clinical manifestation and array of culprit molecular lesions. Correlations between phenotype and genotype remain poorly defined. This review examines the genetic landscape discovered to date for this rare condition. The question of a possible oligogenic model of inheritance influencing phenotypic heterogeneity is raised, with discussion of the benefits and challenges of sequencing technology used to enhance discovery in this space. Considerable work lies ahead in order to achieve diagnostic and prognostic precision and subsequently provide targeted management to this complex cohort of patients.",

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AU - McFadyen, James D.

AU - Perkins, Andrew C.

AU - Tran, Huyen A.

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AB - Congenital fibrinogen disorders or CFDs are heterogenous, both in clinical manifestation and array of culprit molecular lesions. Correlations between phenotype and genotype remain poorly defined. This review examines the genetic landscape discovered to date for this rare condition. The question of a possible oligogenic model of inheritance influencing phenotypic heterogeneity is raised, with discussion of the benefits and challenges of sequencing technology used to enhance discovery in this space. Considerable work lies ahead in order to achieve diagnostic and prognostic precision and subsequently provide targeted management to this complex cohort of patients.

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KW - hypofibrinogenemia

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Congenital fibrinogen disorders—Strengthening genotype–phenotype correlations through novel genetic diagnostic tools

Abstract

Keywords

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Variants leading to dysfibrinogenaemia in the fibrinogen α-chain at residue Arg19 are not solely associated with bleeding, but also with thrombotic events—RESPONSE

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