G6PD Nara: A New Class 1 Glucose-6-Phosphate Dehydrogenase Variant With an Eight Amino Acid Deletion

• Published in: Blood Vol. 82; no. 11; pp. 3250 - 3252
• Main Authors: Hirono, Akira, Fujii, Hisaichi, Shima, Masayuki, Miwa, Shiro
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.1993; The Americain Society of Hematology
• Subjects: Amino Acid Sequence; Anemias. Hemoglobinopathies; Base Sequence; Biological and medical sciences; Child; Diseases of red blood cells; Exons; Gene Deletion; Glucosephosphate Dehydrogenase - genetics; Hematologic and hematopoietic diseases; Humans; Japan; Male; Medical sciences; Molecular Sequence Data; Mutation; Japan; Human; Glucose-6-phosphate 1-dehydrogenase; Hemolytic anemia; Enzyme; Deficiency; Exploration; Hemopathy; Oxidoreductases; Molecular biology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V82.11.3250.3250

In the course of molecular studies on Japanese glucose-6-phosphate dehydrogenase (G6PD) variants using single-strand conformation polymorphisms (SSCP) analysis, we found an unusual class 1 G6PD variant that had nucleotide deletion in exon 9. The patient showed chronic nonspherocytic hemolytic anemia associated with frequent episodes of severe hemolytic attack. The hemolysate exhibited no measurable activity. Although the partially purified enzyme had detectable activity, we could not perform kinetic studies because of its extreme instability. Nucleotide sequencing showed a unique 24 bp deletion at nucleotide 953-976 that predicts an eight amino acid deletion of TKGYLDDP at residue 319-326. While this is one of the most drastic structural alterations found in G6PD variants, the region with the amino acid deletion was distant from both the G6P and NADP+ binding sites and was located in a domain with low sequence homology among species. The comparatively low functional importance of the deleted region may have saved the patient from lethal tissue dysfunction.