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
1   Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain
,
Rocío Benito
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
María Luisa Lozano
3   Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
,
Ana Marín-Quilez
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
Kamila Janusz
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
Marta Martín-Izquierdo
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
Jesús Hernández-Sánchez
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
Veronica Palma-Barqueros
3   Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
,
Jesús María Hernández-Rivas
1   Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain
2   IBSAL, IBMCC, CIC, Universidad de Salamanca-CSIC, Salamanca, Spain
,
José Rivera*
3   Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain
,
José Ramón González-Porras*
1   Department of Hematology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain
› Author Affiliations
Further Information

Publication History

Publication Date:
30 April 2019 (online)

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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.

* Both authors have contributed to the manuscript in similar way.


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