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Published on: August 15, 2019
Biallelic loss-of-function mutations in BPNT1 cause vitamin B12-dependent megaloblastic anemia.
Yi-Heng Zeng1, Yun-Hong Li1, Ru-Ying Yuan1
1First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Blood
|May 21, 2026
Summary
Biallelic loss-of-function mutations in the BPNT1 gene cause vitamin B12-dependent megaloblastic anemia. This deficiency leads to PAP accumulation, impaired ribosome production, and reduced cubam receptor expression.
Area of Science:
- Genetics
- Biochemistry
- Hematology
Background:
- Recurrent megaloblastic anemia can have various underlying causes.
- Vitamin B12 deficiency is a known cause of megaloblastic anemia.
- The genetic basis for some forms of vitamin B12-dependent megaloblastic anemia remains unclear.
Purpose of the Study:
- To identify the genetic cause of recurrent vitamin B12-dependent megaloblastic anemia in affected patients.
- To elucidate the molecular mechanisms underlying BPNT1 deficiency in this condition.
Main Methods:
- Genetic sequencing to identify mutations in patients.
- Biochemical assays to measure metabolite levels (e.g., PAP).
- Analysis of ribosome biogenesis and gene expression in cell or animal models (Bpnt1-null mice).
Main Results:
- Identified biallelic loss-of-function BPNT1 mutations in three patients with vitamin B12-dependent megaloblastic anemia.
- Demonstrated that BPNT1 deficiency leads to the accumulation of 3'-phosphoadenosine 5'-phosphate (PAP).
- Observed impaired ribosome biogenesis and reduced ileal expression of the cubam receptor complex in Bpnt1-null mice.
Conclusions:
- BPNT1 mutations are a novel cause of vitamin B12-dependent megaloblastic anemia.
- BPNT1 deficiency disrupts cellular processes critical for red blood cell formation and nutrient absorption.
- Understanding these mechanisms may inform future therapeutic strategies for related anemias.
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