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Molecular study of sticky platelet syndrome using exome sequencing
Estudio molecular del síndrome de plaqueta pegajosa mediante secuenciación del exoma
Palabras clave:
Thrombosis, Platelet Membrane Glycoproteins, Platelet aggregation, Whole Exome Sequencing (en)Trombosis, Glicoproteínas de membrana plaquetaria, Agregación plaquetaria, Secuenciación del exoma completo (es)
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Introduction: Sticky platelet syndrome (SPS) is a prothrombotic condition characterized by increased platelet aggregation that causes arterial and venous thrombosis. Its diagnosis is reached by identifying increased aggregation using low concentrations of adenosine diphosphate and epinephrine in platelet aggregation tests.
Objectives: To identify common mutations through exome sequencing in two patients from the same family diagnosed with SPS and, thus, contribute to the molecular study of this disease.
Materials and methods: Descriptive study. In January 2018, exome sequencing was performed in a 10-year-old patient treated at Fundación HOMI (Bogotá D.C., Colombia), index case, and in one of his adult first-degree relatives, both with a history of thrombotic disease and diagnosed with SPS. Exome sequencing was performed at the Complexo Hospitalario Universitario de Santiago de Compostela (Spain) using the SureSelect Clinical Research Exome V2 software by Agilent.
Results: Exome sequencing led to detect genetic variants in both cases when compared with the reference sequence. The following variant was identified in the two samples: a cytosine to thymine transition at position c.236 (NM_000174.4) of the glycoprotein (GP)Ib-IX-V complex platelet membrane receptor, which causes a heterozygous transition of the amino acid threonine to isoleucine (i.e., a transition from hydrophilic amino acid to a hydrophobic amino acid) at position p. 79 of the extracellular leucine-rich repeat domain of GPIbα subunit of the (GP)Ib–IX complex, involving a conformational change of the main receptor of ligands IB alpha, which might result in platelet hyperaggregation and thrombosis. This variant has not been described in patients with SPS to date.
Conclusion: The mutation identified in both samples could be related to SPS considering the importance of glycoprotein IX in platelet function.
Introducción. El síndrome de plaqueta pegajosa (SPP) es una condición protrombótica caracterizada por un incremento de la agregabilidad plaquetaria que causa trombosis arterial y venosa. Su diagnóstico se realiza al identificar el aumento de la agregabilidad utilizando bajas concentraciones de adenosín difosfato y epinefrina en pruebas de agregación plaquetaria.
Objetivos. Identificar mutaciones comunes mediante secuenciación del exoma en dos pacientes de una misma familia con diagnóstico de SPP y, de esta forma, contribuir al estudio molecular de esta enfermedad.
Materiales y métodos. Estudio descriptivo en el que se realizó secuenciación del exoma en un paciente de 10 años atendido en la Fundación HOMI (Bogotá, Colombia), caso índice, y en uno de sus familiares adultos en primer grado, ambos con antecedente de enfermedad trombótica y diagnosticados con SPP. La secuenciación del exoma se realizó en el Complexo Hospitalario Universitario de Santiago de Compostela (España) con el programa SureSelect Clinical Research Exome V2 de Agilent.
Resultados. En la secuenciación del exoma se detectaron variantes genéticas en ambos casos en comparación con la secuencia de referencia. En las muestras de ambos pacientes se identificó una variante heterocigota consistente en una transición de citosina a timina en la posición c.236 (NM_000174.4) que provoca el cambio del aminoácido treonina por isoleucina en la posición p.79 del dominio extracelular repetitivo rico en leucina (subunidad GPIbα del complejo de la glicoproteína Ib-IX-V) y que podría provocar el cambio conformacional del receptor principal del ligando Ib alfa, así como hiperagregación plaquetaria y trombosis. Esta variante no ha sido descrita previamente en pacientes con SPP.
Conclusión. La mutación identificada en las muestras estudiadas podría estar relacionada con el SPP considerando la importancia de la glicoproteína IX en las funciones plaquetarias.
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Derechos de autor 2021 Revista de la Facultad de Medicina
Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.
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