A novel PKLR gene mutation identified using advanced molecular techniques

Abstract

This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The proband received cord blood and bone marrow from the second child of the mother for hematopoietic stem cell transplantation and achieved normal hematopoiesis. The genetic characterization analysis and genotype-phenotype correlation study of PKLR gene suggested that NGS was an effective method to confirm the molecular diagnosis of intractable hemolytic anemia. The identification of the mutation aided in prenatal diagnosis in the second pregnancy and the effective clinical management of the affected family.

Pyruvate kinase deficiency: epidemiology, molecular analyses and modern diagnostic approaches (literature review)

“…Первый случай дефицита пируваткиназы был зарегистрирован в 1961 г. [7], на сегодняшний день есть данные о распространенности заболевания во всем мире. Точные данные о частоте встречаемости дефицита пируваткиназы отсутствуют, однако предположительная частота варьирует от 3:1 000 000 до 1:20 000 [8].…”

“…Доказательства протективного эффекта были получены в исследованиях на моделях мышей с малярией, кроме того, снижение репликации малярийного плазмодия в эритроцитах и усиление фагоцитоза зараженных эритроцитов описано у пациентов с дефицитом пируваткиназы [2,8,16]. Среди населения Китая зарегистрированы только спорадические случаи заболевания [7].…”

The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper

“…The use of next-generation sequencing (NGS) in the diagnosis of rare inherited anaemias is increasingly common, as evidenced by a growing number of publications describing its clinical utility. [1][2][3][4][5][6] Excluding disorders of globin synthesis, rare anaemias include Diamond-Blackfan anaemia (DBA), congenital dyserythropoietic anaemias (CDA), congenital sideroblastic anaemias (CSA), and disorders of red cell membrane and enzymes. Other forms of genetic anaemias can also be considered while establishing NGS panels, in particular genetic syndromes, where anaemia comprises one of the constellation of symptoms.…”

The use of next‐generation sequencing in the diagnosis of rare inherited anaemias: A Joint BSH/EHA Good Practice Paper*

“…The use of next‐generation sequencing (NGS) in the diagnosis of rare inherited anaemias is increasingly common, as evidenced by a growing number of publications describing its clinical utility 1–6 . Excluding disorders of globin synthesis, rare anaemias include Diamond–Blackfan anaemia (DBA), congenital dyserythropoietic anaemias (CDA), congenital sideroblastic anaemias (CSA) and disorders of red cell membrane and enzymes.…”