Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia

Abstract

We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia. In neither case was psychomotor impairment observed. The first patient was found to be a compound heterozygote for 2 different missense mutations, 118G>A (Gly40Arg) and 190G>A (Gly64Arg) (cDNA sequence first described by Matsuura et al, 1989). The second patient was homozygous for an in-frame deletion (GAC) from nucleotide (

Red cell adenylate kinase deficiency in India: identification of two novel missense mutations (c.71A>G and c.413G>A)

“…In this report, we have investigated molecular defect of AK deficiency in a 6-year-old male child from Indian origin born of a nonconsanguineous marriage. In our case, the clinical presentation was very similar with the previously reported cases without mental and psychomotor retardation 14. The psychomotor impairment is generally associated with AK deficiency, although the mechanisms responsible are not well understood.…”

Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase

“…This enzyme coordinates different signaling pathways, ensuring adequate response to a broad range of functional, environmental and stress stimuli. In such a way, AK plays a key role in the cell and its dysfunction is connected to the onset of several human diseases, such as heart failure, metabolic disorders, cancer and neurodegenerative diseases 1 2 .…”

Rare hereditary nonspherocytic hemolytic anemia caused by novel homozygous mutation, c.301C>A, (Q101K) in the AK1 gene in an Indian family

“…Now as days, conventional Sanger sequencing, is generally used in a routine diagnostic tool for many genetic disorders but has its limitation in identifying de novo mutations whereas the variant is very rare and that is located outside of the captured regions, NGS targeted panel is very useful for identifying rare blood disorder. NGS has a higher diagnostic value as it has high accuracy and rapidly adapted in the genetic analysis [9]. Therefore, we used a targeted NGS panel for the analysis of 100 genes responsible for rare congenital anaemias, which successfully helped in identifying novel mutations in the AK1 gene in Indian patients.…”

“…The panel mainly includes targeted genes that are associated with red cell haemolglobinopathies, enzymopathies, red cell membrane disorders, congenital dyserythropoietic anaemias, and bone marrow failure syndromes. These NGS gene panels covered a sequence of coding regions, splice site junctions, and deep intronic regions, and regulatory regions, which has the advantages to overcome all the problems in the diagnosis of unexplained haemolytic anaemia cases, especially in identifying de novo mutations [9]. This NGS panel gives fast and accurate results for identifying the genetic diagnosis in patients with unexplained congenital haemolytic anaemia.…”