| Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype? | |
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MedLine Citation:
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PMID: 18247425 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Costello syndrome is a rare congenital disorder typically characterized by severe failure-to-thrive, cardiac abnormalities including tachyarrhythmia and hypertrophic cardiomyopathy, distinctive facial features, a predisposition to papillomata and malignant tumors, neurologic abnormalities, developmental delay, and mental retardation. Its underlying cause is de novo germline mutations in the oncogene HRAS. Almost all Costello syndrome mutations affect one of the glycine residues in position 12 or 13 of the protein product. More than 80% of patients with Costello syndrome share the same underlying mutation, resulting in a G12S amino acid change. We report on two patients with novel HRAS mutations affecting amino acids 58 (T58I) and 146 (A146V), respectively. Despite facial features that appear less coarse than those typically seen in Costello patients, both patients show many of the physical and developmental problems characteristic for Costello syndrome. These novel HRAS mutations may be less common than the frequently reported G12S change, or patients with these changes may be undiagnosed due to their less coarse facial features. In addition to the findings previously known to occur in Costello syndrome, one of our patients had hypertrophic pyloric stenosis. This led us to review the medical histories on a cohort of proven HRAS mutation positive Costello syndrome patients, and we found a statistically significantly (P < 0.001) increased frequency of pyloric stenosis in Costello syndrome (5/58) compared to the general population frequency of 2-3/1,000. Thus we add hypertrophic pyloric stenosis to the abnormalities seen with increased frequency in Costello syndrome. |
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Authors:
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Karen W Gripp; A Micheil Innes; Marni E Axelrad; Tanya L Gillan; Jillian S Parboosingh; Christine Davies; Norma J Leonard; Monique Lapointe; Daniel Doyle; Sarah Catalano; Linda Nicholson; Deborah L Stabley; Katia Sol-Church |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: American journal of medical genetics. Part A Volume: 146A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-03-03 Completed Date: 2008-04-16 Revised Date: 2008-05-29 |
Medline Journal Info:
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Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
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Languages: eng Pagination: 683-90 Citation Subset: IM |
Copyright Information:
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(c) 2008 Wiley-Liss, Inc. |
Affiliation:
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Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, Delaware 19899, USA. kgripp@nemours.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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diagnosis*,
genetics Base Sequence Child Child, Preschool Cognition / physiology DNA Mutational Analysis Developmental Disabilities / complications, diagnosis*, genetics Facial Asymmetry / complications, congenital*, genetics Female Germ-Line Mutation* Humans Infant Male Proto-Oncogene Proteins p21(ras) / genetics* Psychological Tests Pyloric Stenosis / complications, diagnosis Syndrome |
| Grant Support | |
ID/Acronym/Agency:
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4P20 RR020173-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.6.5.2/HRAS protein, human; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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