ArticleThe Journal of clinical investigation2017
Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Contemporary Approach to the Diagnosis and Classification of Myelodysplastic Neoplasms/Syndromes-Recommendations From the International Consortium for Myelodysplastic Neoplasms/Syndromes (MDS [icMDS]).Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Guideline
- ConstitutionalHaematologica · 2018Trial
- Structural mechanisms of SAMD9 autoinhibition and pathogenic dysregulation.Science advances · 2026Article
- Long-term survival in MIRAGE syndrome: Insights into systemic manifestations and management with review of literature.Endocrine journal · 2026Review
- A specific stem cell program and CD112 immunological axis dysfunctions underpinning monosomy 7-associated myeloid neoplasms.Signal transduction and targeted therapy · 2026Article
- Carrier screening in the reproductive setting-Are there medical implications for the heterozygote?-A guide for clinicians.Pregnancy (Hoboken, N.J.) · 2026Review
- Disease insights from brain somatic mosaicism.Experimental & molecular medicine · 2026Review
- Moving Beyond Somatic Alterations: Uncovering the Germline Basis of Myeloid Malignancies.Cancers · 2026Review
- Case Report: Unveiling the enigma: a rare male neonatal case of MIRAGE syndrome with female external genital presentation and literature review.Frontiers in pediatrics · 2026Article
- Case Report: Growth hormone deficiency and response to treatment in MIRAGE syndrome: expanding the endocrine phenotype.Frontiers in endocrinology · 2026Article
- Case Report: Hidden B-cell dysregulation in MIRAGE syndrome.Frontiers in pediatrics · 2026Article
- A De Novo Mutation (c.2423A>G) inHuman mutation · 2026Article
- Evolution of SAMD9 and SAMD9L genes in primates: a complex history of gene loss, gene duplication and pseudogenization.Immunogenetics · 2025Article
- Normal Immune Function in a Newborn With Early Identification of aClinical case reports · 2025Article
- Germline and somatic genetic landscape of pediatric myelodysplastic syndromes.Haematologica · 2025Review
- Poxvirus Host-Range Determinants: SAMD9/9L and Beyond.Annual review of virology · 2025Review
- Detecting likely germline variants during tumor-based molecular profiling.The Journal of clinical investigation · 2025Review
- Review
- Article
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 17 institutions in 6 countries.
Funding
Abstract
It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain-containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (-7), deletions of 7q (7q-), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with -7 and 7q- developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.