ArticleAmerican journal of human genetics2020
Bi-allelic Mutations in NADSYN1 Cause Multiple Organ Defects and Expand the Genotypic Spectrum of Congenital NAD Deficiency Disorders.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 48 citations in OpenAlex.
- Enhanced Imaging in Bladder Cancer: Fluorescence Cystoscopy and Molecular Diagnostics.Life (Basel, Switzerland) · 2026Article
- Nicotinamide salvage is required for proliferation and sustaining self-renewal in undifferentiated embryonic stem cells.Stem cells (Dayton, Ohio) · 2026Article
- Timing of NAD Deficiency During Organogenesis Dictates Defect Type and Penetrance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Discovery and annotation of putative genes and novel RNA splice-isoforms in the human heart.Frontiers in cardiovascular medicine · 2026Article
- Maternal Circulatory NAD Precursor Levels and the Yolk Sac Determine NAD Deficiency-Driven Congenital Malformation Risk.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Recessive genetic contribution to congenital heart disease in 5,424 probands.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Impaired yolk sac NAD metabolism disrupts murine embryogenesis with relevance to human birth defects.eLife · 2025Article
- A zebrafish model of nicotinamide adenine dinucleotide (NADbioRxiv : the preprint server for biology · 2025Article
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations.American journal of human genetics · 2024Article
- Supplementation with NAD+ and its precursors: A rescue of female reproductive diseases.Biochemistry and biophysics reports · 2024Review
- A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder.The Journal of clinical investigation · 2024Article
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- Metabolic Alterations in NADSYN1-Deficient Cells.Metabolites · 2023Article
- CRISPR-based knockout and base editing confirm the role of MYRF in heart development and congenital heart disease.Disease models & mechanisms · 2023Article
- Maternal heterozygosity of Slc6a19 causes metabolic perturbation and congenital NAD deficiency disorder in mice.Disease models & mechanisms · 2023Article
- NAD+ deficiency in human congenital malformations and miscarriage: A new model of pleiotropy.American journal of medical genetics. Part A · 2022Article
- Identification ofDiagnostics (Basel, Switzerland) · 2022Article
- A novelExperimental and therapeutic medicine · 2022Article
- Integrating RNA-seq and scRNA-seq to explore the biological significance of NAD + metabolism-related genes in the initial diagnosis and relapse of childhood B-cell acute lymphoblastic leukemia.Frontiers in immunology · 2022Article
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Authors and funding
16 authors at 6 institutions in 4 countries.
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Abstract
Birth defects occur in up to 3% of all live births and are the leading cause of infant death. Here we present five individuals from four unrelated families, individuals who share similar phenotypes with disease-causal bi-allelic variants in NADSYN1, encoding NAD synthetase 1, the final enzyme of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway. Defects range from the isolated absence of both kidneys to multiple malformations of the vertebrae, heart, limbs, and kidney, and no affected individual survived for more than three months postnatally. NAD is an essential coenzyme for numerous cellular processes. Bi-allelic loss-of-function mutations in genes required for the de novo synthesis of NAD were previously identified in individuals with multiple congenital abnormalities affecting the heart, kidney, vertebrae, and limbs. Functional assessments of NADSYN1 missense variants, through a combination of yeast complementation and enzymatic assays, show impaired enzymatic activity and severely reduced NAD levels. Thus, NADSYN1 represents an additional gene required for NAD synthesis during embryogenesis, and NADSYN1 has bi-allelic missense variants that cause NAD deficiency-dependent malformations. Our findings expand the genotypic spectrum of congenital NAD deficiency disorders and further implicate mutation of additional genes involved in de novo NAD synthesis as potential causes of complex birth defects.
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