Somatic mosaicism for an HRAS mutation causes Costello syndrome.

Somatic mosaicism for an HRAS mutation causes Costello syndrome. Research Abstract Details 

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Somatic mosaicism for an HRAS mutation causes Costello syndrome. Abstract Text:

Karen W Gripp,Deborah L Stabley,Linda Nicholson,Jodi D Hoffman,Katia Sol-Church,

De novo heterozygous HRAS point mutations have been reported in more than 81 patients with Costello syndrome (CS), but genotype/phenotype correlation remains incomplete because the majority of patients share a common mutation, G12S, seen in 65/81 (80%). Somatic HRAS mutations have previously been identified in solid tumors, and mutation hot spots related to a gain-of-function effect of the gene product are known. The germline mutations causing CS occur at these hot spots and convey a gain-of-function effect, thus accounting for the greatly increased cancer risk. Diagnostic testing for HRAS mutations is now available and the identification of a mutation in a patient with consistent clinical findings confirms a diagnosis of CS. It is not clear yet if the absence of an HRAS mutation precludes a diagnosis of CS. Because there is a significant overlap in the clinical findings of Costello, cardio-facio-cutaneous, and Noonan syndromes, diagnostic uncertainty remains in patients lacking an HRAS mutation. We report here on a female with findings suggestive of CS in whom mutation analysis performed with standard techniques on white blood cell derived DNA did not show an HRAS mutation. However, analysis of DNA derived from three independently collected buccal swabs showed a sequence change qualitatively consistent with the G12S mutation. Allelic quantitation showed the presence of the mutation in approximately 25%-30% of the sampled buccal cells. In this patient, standard technology failed to identify the disease causing mutation on DNA derived from a blood sample, highlighting the potential pitfalls in the interpretation of negative mutation studies. This is the first reported CS patient mosaic for the common HRAS mutation, likely due to a somatic mutation occurring very early in fetal development.

Somatic mosaicism for an HRAS mutation causes Costello syndrome. Publishing Authors By Initials

KW Gripp,DL Stabley,L Nicholson,JD Hoffman,K Sol-Church,

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Somatic mosaicism for an HRAS mutation causes Costello syndrome. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of medical genetics. Part A

VOLUME: 140

Page Numbers: 2163-9

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ISSN: 1552-4825

DAY: 15

MONTH: Oct

YEAR: 2006

Somatic mosaicism for an HRAS mutation causes Costello syndrome. Information

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LANGUAGE: eng

NlmUniqueID: 101235741

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Grant and Affiliation Information for Somatic mosaicism for an HRAS mutation causes Costello syndrome.

AFFILIATION: Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, Delaware 19899, USA. kgripp@nemours.org

Country: United States

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MEDLINETA: Am J Med Genet A

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