Molecular Diagnosis of Inherited Coagulation and Bleeding Disorders

José María Bastida; Rocío Benito; María Luisa Lozano; Ana Marín-Quilez; Kamila Janusz; Marta Martín-Izquierdo; Jesús Hernández-Sánchez; Veronica Palma-Barqueros; Jesús María Hernández-Rivas; José Rivera; José Ramón González-Porras

doi:10.1055/s-0039-1687889

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2019; 45(07): 695-707
DOI: 10.1055/s-0039-1687889

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Molecular Diagnosis of Inherited Coagulation and Bleeding Disorders

José María Bastida

¹Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain

,

Rocío Benito

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

María Luisa Lozano

³Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain

,

Ana Marín-Quilez

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

Kamila Janusz

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

Marta Martín-Izquierdo

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

Jesús Hernández-Sánchez

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

Veronica Palma-Barqueros

³Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain

,

Jesús María Hernández-Rivas

¹Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain

²IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain

,

José Rivera^*

³Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain

,

José Ramón González-Porras^*

¹Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain

› Author Affiliations

Abstract

Diagnosis of inherited bleeding disorders (IBDs) remains challenging, especially in the case of inherited platelet disorders, due to the heterogeneity of the clinical and laboratory phenotype, the limited specificity of platelet function tests, and the large number of potential culprit genes. Unraveling the underlying molecular defect provides the definitive diagnosis of IBDs, facilitating prognosis and clinical care, which are especially important for severe clinical syndromes and those that may be associated with an increased risk of malignancy. Until recently, Sanger sequencing of candidate genes has been the only method of molecular diagnosis, but this approach is time-consuming and costly and requires phenotype-based identification of any obvious candidate gene(s). Nowadays, high-throughput sequencing (HTS) allows the simultaneous and rapid investigation of multiple genes at a manageable cost. This HTS technology that includes targeted sequencing of prespecified genes, whole-exome sequencing, or whole-genome sequencing, is revolutionizing the genetic diagnosis of human diseases. Through its extensive implementation in research and clinical practice, HTS is rapidly improving the molecular characterization of IBDs. However, despite the availability of this powerful approach, many patients still do not receive a diagnosis. As IBDs are complex and rare diseases, development of more advanced laboratory assays, improvements in bioinformatic pipelines, and the formation of multidisciplinary teams are encouraged to advance our understanding of IBDs.

Keywords

molecular diagnosis - inherited platelet disorders - inherited rare bleeding disorders - high-throughput sequencing

Full Text

References

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Supplementary Material

Supplementary Material