NOONAN SYNDROME AND RELATED DISORDERS: Genetics and Pathogenesis
Abstract
▪ Abstract Noonan syndrome is a pleiomorphic autosomal dominant disorder with short stature, facial dysmorphia, webbed neck, and heart defects. In the past decade, progress has been made in elucidating the pathogenesis of this disorder using a positional cloning approach. Noonan syndrome is now known to be a genetically heterogeneous disorder with nearly one half of cases caused by gain-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2. Similar germ line mutations cause two related genetic disorders, Noonan-like disorder with multiple giant cell lesion syndrome and LEOPARD syndrome, and somatic PTPN11 mutations can underlie certain pediatric hematopoietic malignancies, including juvenile myelomonocytic, acute lymphoblastic, and acute myelogenous leukemias. A mouse model of PTPN11-related Noonan syndrome was recently generated, providing a reagent for studying disease pathogenesis in greater depth as well as experimenting with novel therapeutic strategies.
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Loss-of-function as well as gain-of-function mutations and/or overexpression of SHP2 are found in various diseases such as different cancer types, Noonan syndrome, and LEOPARD syndrome.
“Loss-of-function as well as gain-of-function mutations and/or overexpression of SHP2 are found in various diseases such as different cancer types [49], Noonan- [50], and LEOPARD-syndrome [51].”
From The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling (2021) · cites this paper as [50]
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References 98 · Cited by 355
- Authors
- Tartaglia, M., & Gelb, B. D.
- Affiliations
- Istituto Superiore di Sanità (IT)
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Annual Review of Genomics and Human Genetics
- Publisher
- Annual Reviews
- Published
- 2005-09-01
- Volume
- 6
- Issue
- 1
- Pages
- 45-68
- ISSN
- 1527-8204 (ISSN-L)
- 1545-293X
- OpenAlex
- W2159532830
- Cited by
- 355
- References
- 98
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 8 · 2020: 15 · 2019: 12 · 2018: 7 · 2017: 12 · 2016: 8 · 2015: 13 · 2014: 24 · 2013: 20 · 2012: 16
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Genomics and Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50hl074728-05)
- National Heart, Lung, and Blood Institute (HL 074728, HL 71207, R01HL071207)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD01294, K24HD001294)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- Noonan syndrome, LEOPARD syndrome, PTPN11, SHP2, protein tyrosine phosphatase, gain-of-function mutations, autosomal dominant disorder, genetic heterogeneity, congenital heart disease, short stature, facial dysmorphism, webbed neck, juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, mouse model, pathogenesis
- MeSH terms
- Animals, Female, Genotype, Humans, Leukemia, Genetic Linkage, Male, Models, Molecular, Mutation, Noonan Syndrome, Paternal Age, Phenotype, Protein Tyrosine Phosphatases, Intracellular Signaling Peptides and Proteins, History, 19th Century, History, 20th Century, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 11
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