title: 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 (nt) 498 to 500 or nt 501 to 503 of the cDNA sequence, predicting deletion of either aspartic acid (Asp) 140 or 141. The crystal structure of porcine cytosolic AK was used as a molecular model to investigate how these mutations may affect enzyme structure and function.
authors.affiliation: Red Cell Patholology Unit, ICMHO-IDIBAPS, Hospital Clinic i Provincial, Villarroel 170, 08036-Barcelona, Spain. jlvives@medicina.ub.es
authors.forename: Joan-Lluis Vives
authors.initials: JL
authors.lastname: Corrons
authors.forename: Estefania
authors.initials: E
authors.lastname: Garcia
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Tusell
authors.forename: Kottayil I
authors.initials: KI
authors.lastname: Varughese
authors.forename: Carol
authors.initials: C
authors.lastname: West
authors.forename: Ernest
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000263:Adenylate Kinase / Q000172:deficiency*; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics*; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D007223:Infant; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D000263:Adenylate Kinase