Hereditary non-spherocytic hemolytic anemia and severe glucose phosphate isomerase deficiency in an Indian patient homozygous for the L487F mutation in the human GPI gene.
Homozygous glucose phosphate isomerase (GPI) deficiency is one of the most important erythroenzymopathies causing hereditary non-spherocytic hemolytic anemia (HNSHA). We report an Indian patient with HNSHA showing 85 % reduction in GPI activity resulting from a homozygous missense replacement g.1459C > T in exon 16, leading to a substitution of the protein residue L487F mutation. This mutation has been detected previously in a compound heterozygous state along with another mutation in a GPI deficient patient elsewhere. To our knowledge, this is the first report of HNSHA associated with GPI deficiency with the homozygous L487F mutation, as well as the first report from India of GPI deficiency. Molecular modeling using the human crystal structure of GPI as a model was performed to determine how this mutation could affect enzyme structure and function. The enzyme is present in a dimeric form necessary for normal activity; the L487F mutation causes a loss of the ability of GPI to dimerize, which decreases the thermostability of the enzyme and results in significant changes in erythrocyte metabolism.
Department of Haematogenetics, National Institute of Immunohaematology, Indian Council of Medical Research, 13th Floor, New Multistoried Building, K.E.M Hospital Campus, Parel, Mumbai, 400012, India.
Prashant
P
Warang
Prabhakar
P
Kedar
Kanjaksha
K
Ghosh
Roshan B
RB
Colah
D000293:Adolescent; D000328:Adult; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D044465:White People / Q000235:genetics*; D055815:Young Adult
D005956:Glucose-6-Phosphate Isomerase