Biallelic loss-of-function mutations in <i>BPNT1</i> cause vitamin B12–dependent megaloblastic anemia

Y Yi-Heng Zeng (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) Y Yun-Hong Li (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) R Ru-Ying Yuan (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) D Dan-Dan Zuo (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) X Xiao-Sheng Zheng (4Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China) W Wen-Hao Xiao (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) M Min-Kun Fang (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) B Bin-Bin Lin (1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China) C Chun-Yan Cao (6Department of Neurology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China) X Xue-Wen Cheng (7Lin Gang Laboratory, Shanghai, China) N Ning Wang T Ting Yang (Key Laboratory for Soft Chemistry and Functional Materials of Ministry Education, School of Chemistry and Chemical Engineering) W Wei Luo W Wan-Jin Chen

Abstract

Abstract We identified biallelic loss-of-function BPNT1 mutations in 3 patients with recurrent vitamin B12–dependent megaloblastic anemia. Mechanistically, BPNT1 deficiency caused the accumulation of PAP (3′-phosphoadenosine 5′-phosphate), impaired ribosome biogenesis, and reduced ileal expression of the cubilin/amnionless receptor complex in Bpnt1-null mice.

Article Details

Journal Blood
Volume / Issue Vol. 148, Issue 5
Published July 30, 2026
Pages 634-638
ISSN 0006-4971
Publisher Elsevier BV

Journal Info

Blood

Elsevier BV

ISSN: 0006-4971 Health Sciences

Authors (14)

Y

Yi-Heng Zeng

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

Y

Yun-Hong Li

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

R

Ru-Ying Yuan

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

D

Dan-Dan Zuo

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

X

Xiao-Sheng Zheng

4Department of Neurology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

W

Wen-Hao Xiao

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

M

Min-Kun Fang

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

B

Bin-Bin Lin

1Department of Neurology, Fujian Institute of Neurology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China

C

Chun-Yan Cao

6Department of Neurology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China

X

Xue-Wen Cheng

7Lin Gang Laboratory, Shanghai, China

N

Ning Wang

T

Ting Yang

Key Laboratory for Soft Chemistry and Functional Materials of Ministry Education, School of Chemistry and Chemical Engineering

W

Wei Luo

W

Wan-Jin Chen