lunes, 12 de mayo de 2014

Characterization of a Phenotype-Based Genetic... [Mayo Clin Proc. 2014] - PubMed - NCBI

Characterization of a Phenotype-Based Genetic... [Mayo Clin Proc. 2014] - PubMed - NCBI

 2014 Apr 29. pii: S0025-6196(14)00148-7. doi: 10.1016/j.mayocp.2014.01.025. [Epub ahead of print]

Characterization of a Phenotype-Based Genetic Test Prediction Score for Unrelated Patients with Hypertrophic Cardiomyopathy.



To determine the prevalence and spectrum of mutations and genotype-phenotype relationships in the largest hypertrophic cardiomyopathy (HCM) cohort to date and to provide an easy, clinically applicable phenotype-derived score that provides a pretest probability for a positive HCM genetic test result.


Between April 1, 1997, and February 1, 2007, 1053 unrelated patients with the clinical diagnosis of HCM (60% male; mean ± SD age at diagnosis, 44.4±19 years) had HCM genetic testing for the 9 HCM-associated myofilament genes. Phenotyping was performed by review of electronic medical records.


Overall, 359 patients (34%) were genotype positive for a putative HCM-associated mutation in 1 or more HCM-associated genes. Univariate and multivariate analyses identified the echocardiographic reverse curve morphological subtype, an age at diagnosis younger than 45 years, a maximum left ventricular wall thickness of 20 mm or greater, a family history of HCM, and a family history of sudden cardiac death as positive predictors of positive genetic test results, whereas hypertension was a negative predictor. A score, based on the number of predictors of a positive genetic test result, predicted a positive genetic test result ranging from 6% when only hypertension was present to 80% when all 5 positive predictor markers were present.


In this largest HCM cohort published to date, the overall yield of genetic testing was 34%. Although all the patients were diagnosed clinically as having HCM, the presence or absence of 6 simple clinical/echocardiographic markers predicted the likelihood of mutation-positive HCM. Phenotype-guided genetic testing using the Mayo HCM Genotype Predictor score provides an easy tool for an effective genetic counseling session.
Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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