Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant

Chéry, Céline; Hehn, Alain; Mrabet, Nadir T.; Oussalah, Abderrahim; Jeannesson, Élise; Besseau, Cyril; Alberto, Jean-Marc; Groß, Isabelle; Josse, Thomas; Gérard, P.; Guéant-Rodríguez, Rosa María; Freund, Jean–Noël; Devignes, J.; Bourgaud, Frédéric; Peyrin–Biroulet, Laurent; Feillet, François; Guéant, Jean‐Louis

doi:10.1016/j.biochi.2013.01.022

Cited by 22 publications

(27 citation statements)

References 25 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…In congenital IFD, gastric acid secretion is normal and B 12 deficiency results from a mutation in GIF leading to a low level or lack of GIF in gastric juices, abnormal susceptibility of GIF to pepsin degradation, or reduced affinity for ileal GIF-B 12 receptor Chery et al 2013). IFD differs from adulthood-acquired cobalamin deficiencies associated with atrophic gastritis in which normal GIF can be produced but is reduced in quantity due to decreased parietal cells or an autoimmune disorder with production of antibodies against GIF.…”

Section: Amnmentioning

confidence: 99%

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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

et al. 2014

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Intrinsic factor deficiency (OMIM #261000, IFD) is a rare inherited disorder of vitamin B 12 metabolism due to mutations in the gastric intrinsic factor (GIF) gene.We report three individuals from an Old Order Mennonite community who presented with B 12 deficiency. Two cases are siblings born to consanguineous parents and the third case is not known to be closely related. The older male sib presented at 4 years with gastrointestinal symptoms, listlessness, and pallor. He had pancytopenia with megaloblastic anemia. Serum B 12 was 61 (198-615 pmol/L). Methylmalonic aciduria was present. C3 was elevated on acylcarnitine profile. Homocysteine was high at 16.7 (5.0-12.0 umol/L).

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“…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).…”

Section: Discussionmentioning

confidence: 99%

Section: Amnmentioning

confidence: 99%

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

et al. 2014

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“…GIF mutations were screened using the high resolution melting (HRM) quantitative‐polymerase chain reaction (q‐PCR) on a LightCycler 480 (Roche Molecular Biochemicals, Lyon, France) and confirmed by direct sequencing using the dideoxy chain termination reaction. The 9 exons encoding GIF were amplified from genomic DNA . The genotypes of FUT2 polymorphism rs601338 (NM_000511: 461G > A encoding W143X) was determined by real‐time PCR (LightCycler 480), as described .…”

Section: Methodsmentioning

confidence: 99%

“…GIF is a fucosylated glycoprotein secreted by gastric parietal cells and needed for the ileal uptake of B12. The FUT2 rs601338 secretor variant influences the blood level of vitamin B12 and the secretion of GIF . The subjects homozygous for the FUT2 rs601338 non‐secretor variant (GG genotype) have a higher B12 blood level than those with the secretor variant, in large cohorts with levels within the range of normal values .…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the FUT2 GG genotype is associated with a low B12 level and anemia in intrinsic factor deficiency (IFD) cases with the mutated GIF 290TC genotype reported in 3 families and 1 case identified by screening of a large cohort of Italian ambulatory elderly subjects. In these cases with heterozygous GIF mutations, the FUT2 secretor variant worsened the B12 status through impaired secretion of GIF …”

Section: Introductionmentioning

confidence: 99%

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Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects

et al. 2017

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Funding informationRegion of Lorraine (France); Ministry of Health (PHRC COMET) Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/ FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms. K E Y W O R D Sbirth defects, FUT2, gastric intrinsic factor, neural tube defects, 1-carbon metabolism, vitamin B12

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The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review

Wahbeh

Manyama

2021

Intl J of Devlp Neuroscience

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Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case–control studies, 3 cross‐sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo‐transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD‐affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well‐designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.

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Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant

Cited by 22 publications

References 25 publications

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

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

Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects

The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review

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