| Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C. | |
| | |
MedLine Citation:
|
PMID: 21438134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Costello syndrome is characterized by severe failure-to-thrive, short stature, cardiac abnormalities (heart defects, tachyarrhythmia, and hypertrophic cardiomyopathy (HCM)), distinctive facial features, a predisposition to papillomata and malignant tumors, postnatal cerebellar overgrowth resulting in Chiari 1 malformation, and cognitive disabilities. De novo germline mutations in the proto-oncogene HRAS cause Costello syndrome. Most mutations affect the glycine residues in position 12 or 13, and more than 80% of patients share p.G12S. To test the hypothesis that subtle genotype-phenotype differences exist, we report the first cohort comparison between 12 Costello syndrome individuals with p.G13C and individuals with p.G12S. The individuals with p.G13C had many typical findings including polyhydramnios, failure-to-thrive, HCM, macrocephaly with posterior fossa crowding, and developmental delay. Subjectively, their facial features were less coarse. Statistically significant differences included the absence of multifocal atrial tachycardia (P-value = 0.033), ulnar deviation of the wrist (P < 0.001) and papillomata (P = 0.003), and fewer neurosurgical procedures (P = 0.024). Fewer individuals with p.G13C had short stature (height below -2 SD) without use of growth hormone (P < 0.001). The noteworthy absence of malignant tumors did not reach statistical significance. Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair resulting in easily pluckable hair with a matted appearance, different from the tight curls typical for most Costello syndrome individuals. Unusually long eye lashes requiring trimming are a novel finding we termed dolichocilia. These distinctive ectodermal findings suggest a cell type specific effect of this particular mutation. Additional patients are needed to validate these findings. |
| | |
Authors:
|
Karen W Gripp; Elizabeth Hopkins; Katia Sol-Church; Deborah L Stabley; Marni E Axelrad; Daniel Doyle; William B Dobyns; Cindy Hudson; John Johnson; Romano Tenconi; Gail E Graham; Ana Berta Sousa; Raoul Heller; Maria Piccione; Giovanni Corsello; Gail E Herman; Marco Tartaglia; Angela E Lin |
Related Documents
:
|
21480144 - Inferior vena cava obstruction by a cardiac mass: unusual presentation of primary antip... 21257264 - Vaginal allodynia as the presentation of a thalamic tumor. 21314064 - A case report of vinorelbine monotherapy-related acute bronchospasm and non-st elevatio... 22362134 - Modulation of histone deacetylase attenuates naloxone-precipitated opioid withdrawal sy... 7304714 - Purtscher's retinopathy associated with acute pancreatitis. 9048534 - Beta2-agonist induced ventricular dysrhythmias secondary to hyperexcitable conduction s... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-15 |
Journal Detail:
|
Title: American journal of medical genetics. Part A Volume: 155A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-05-13 Completed Date: 2011-08-30 Revised Date: 2011-11-24 |
Medline Journal Info:
|
Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
|
Languages: eng Pagination: 706-16 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
|
Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, Delaware, USA. kgripp@nemours.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Brain / abnormalities Child Child, Preschool Costello Syndrome / complications, diagnosis, genetics* Face / abnormalities Female Heart Defects, Congenital / etiology Humans Infant Magnetic Resonance Imaging Male Musculoskeletal Abnormalities / etiology Mutation / genetics* Neoplasms / etiology Phenotype* Pregnancy Proto-Oncogene Proteins p21(ras) / genetics* Young Adult |
| Grant Support | |
ID/Acronym/Agency:
|
4P20 RR020173-01/RR/NCRR NIH HHS; GGP10020//Telethon |
| Chemical | |
Reg. No./Substance:
|
EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Problems faced when evaluating the bioaccumulation potential of substances under reach.
Next Document: Nosology and classification of genetic skeletal disorders: 2010 revision.