Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency

Abstract

A 4-base deletion has been identified in the coding region of the gene for gastric intrinsic factor (IF) in an 11-year-old girl with severe anemia and cobalamin (Cbl) deficiency. The bone marrow showed frank megaloblastic morphology, and the Schilling test indicated a failure to absorb Cbl that was corrected by coadministration of IF. Pentagastrin administration induced acid secretion, but the gastric juice lacked IF as determined by CbI binding, by fractionation of protein-bound CbI, and by immunoprecipitation with anti-IF antiserum. Individual exons were amplified by the polymerase chain reaction by using primers to the flanking intronic regions, and the nucleotide sequence analysis identified a 4-base deletion (c183_186delGAAT) spanning positions 104 to 107 in exon 2, resulting in premature termination of translation. This mutation also eliminates a site for Bst XI endonuclease and introduces a site for BsaBI for identifying this deletion in hereditary IF deficiency.

Biochemical and Hematologic Manifestations of Gastric Intrinsic Factor (GIF) Deficiency: A Treatable Cause of B12 Deficiency in the Old Order Mennonite Population of Southwestern Ontario

“…IFD resulting from a mutation in GIF was first described in 2004 by Yassin et al in a patient presenting with severe megaloblastic anemia (Yassin et al 2004). Since then, multiple case reports have identified other GIF mutations resulting in B 12 deficiency and megaloblastic anemia.…”

“…With studies demonstrating homozygous and compound heterozygote mutations, the inheritance has been established as autosomal recessive for IFD (Yassin et al 2004;Chery et al 2013).…”

Methylmalonic Acidemia and Megaloblastic Anemia due to Congenital Intrinsic Factor Deficiency

“…Congenital intrinsic factor deficiency has been reported as a rare cause of megaloblastic anemia [1,3]. The genetic testing of the CUBN, GIF, and AMN genes was solely available through a genetic laboratory in Germany.…”

“…IFD is caused by mutations in the gene GIF [3]. Patients with IFD present with pancytopenia and megaloblastic anemia and unlike IGS, cobalamin malabsorption is corrected by intrinsic factor administration [3,4].…”

“…Patients with IFD present with pancytopenia and megaloblastic anemia and unlike IGS, cobalamin malabsorption is corrected by intrinsic factor administration [3,4]. In 2004, a specific GIF mutation was first identified as a cause of severe anemia and cobalamin deficiency in an 11 year old girl [3].…”