scholarly journals Variable Phenotypic Expression Including Late Presentation of Hypertrophic Cardiomyopathy in LEOPARD Syndrome with P.Q510E Mutation in PTPN11 Gene

Author(s):  
Md. Zahidus Sayeed
2006 ◽  
Vol 16 (6) ◽  
pp. 599-601 ◽  
Author(s):  
Giuseppe Limongelli ◽  
Giuseppe Pacileo ◽  
Raffaele Calabrò

We report the sudden cardiac death of a young male presenting with classic clinical features of LEOPARD syndrome, shown to be due to a mutation in the PTPN11 gene, and severe non obstructive hypertrophic cardiomyopathy. We also discuss briefly the usefulness of prophylactic risk stratification in patients with syndromic and non syndromic hypertrophic cardiomyopathy.


Heart ◽  
2011 ◽  
Vol 97 (Suppl 1) ◽  
pp. A95-A95 ◽  
Author(s):  
N. Sheikh ◽  
M. Papadakis ◽  
N. Chandra ◽  
H. Raju ◽  
A. Zaidi ◽  
...  

2008 ◽  
Vol 18 (1) ◽  
pp. 193-201 ◽  
Author(s):  
Kimihiko Oishi ◽  
Hui Zhang ◽  
William J. Gault ◽  
Cindy J. Wang ◽  
Cheryl C. Tan ◽  
...  

2011 ◽  
Vol 4 (1) ◽  
pp. 74 ◽  
Author(s):  
Madhusudan Ganigara ◽  
Atul Prabhu ◽  
RaghvannairSuresh Kumar

Circulation ◽  
2011 ◽  
Vol 124 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Martin S. Maron ◽  
Iacopo Olivotto ◽  
Caitlin Harrigan ◽  
Evan Appelbaum ◽  
C. Michael Gibson ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alex Gyftopoulos ◽  
Yi-Ju Chen ◽  
Libin Wang ◽  
Charles H Williams ◽  
Young Wook Chun ◽  
...  

Introduction: Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiac disease affecting 1:500 to 1:200 individuals worldwide. HCM has a heterogeneous genetic profile and phenotypic expression. More than 1400 known pathogenic variants have been identified in 11 sarcomere genes. In about 40% of HCM patients, the genetic cause may not be identified. The same mutation may lead to different phenotypes and severity in different individuals. Identification of novel HCM genes and modifiers will expand our understanding of the signaling pathways that are responsible for phenotypic expression of HCM. Methods: The UK Biobank comprises clinical and genetic data for greater than 500,000 individuals. We used OASIS, an information system for analyzing, searching, and visualizing associations between phenotype and genotype data to analyze this data. We compared control individuals to HCM individuals identified by ICD-10 code (I42.1 and I42.2) in a 20-to-1 fashion. Related individuals and those with confounding diagnoses were excluded. Results: The analysis was performed with Plink’s GLM option, and we identified 84 variants with a minor allele frequency of 0.5% or greater in 65 genes associated with HCM with a p < 1x10 -6 , including 4 with p < 5x10 -8 . The identified genes encode lncRNAs, miRNAs, and membrane proteins. Variants with high significance were identified in the genes encoding putative ciliary components DNAL4 (dynein axonemal light chain 4; p = 2.9x10 -8 ), MYO1D (unconventional myosin 1D; p = 3.1x10 -8 ), ITFAP (intraflagellar transport associated protein; p = 9.5x10 -8 ), CABCOCO1 (ciliary associated calcium biding coiled-coil 1; p = 3.7x 10 -7 ), EVL (Enah-Vasp-like; p = 4.4x 10 -7 ) and IFT122 (intraflagellar transport 122; p = 8.0 x10 -7 ). Conclusion: While none of these have previously associated with HCM, our findings suggest ciliary structure and function may play a role in disease manifestation. Our method is unique by pooling individuals in a large population set to identify potential causative or contributing mutations. Bioinformatic tools, such as OASIS, allow for the identification of previously unrecognized variants that may play a role in the development of HCM. This approach has identified numerous novel genes as possible risk loci.


Open Heart ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. e001220
Author(s):  
Berglind Adalsteinsdottir ◽  
Michael Burke ◽  
Barry J Maron ◽  
Ragnar Danielsen ◽  
Begoña Lopez ◽  
...  

ObjectiveThe myosin-binding protein C (MYBPC3) c.927-2A>G founder mutation accounts for >90% of sarcomeric hypertrophic cardiomyopathy (HCM) in Iceland. This cross-sectional observational study explored the penetrance and phenotypic burden among carriers of this single, prevalent founder mutation.MethodsWe studied 60 probands with HCM caused by MYBPC3 c.927-2A>G and 225 first-degree relatives. All participants underwent comprehensive clinical evaluation and relatives were genotyped.ResultsGenetic and clinical evaluation of relatives identified 49 genotype-positive (G+) relatives with left ventricular hypertrophy (G+/LVH+), 59 G+without LVH (G+/LVH−) and 117 genotype-negative relatives (unaffected). Compared with HCM probands, G+/LVH+ relatives were older at HCM diagnosis, had less LVH, a less prevalent diastolic dysfunction, fewer ECG abnormalities, lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I levels, and fewer symptoms. The penetrance of HCM was influenced by age and sex; specifically, LVH was present in 39% of G+males but only 9% of G+females under age 40 years (p=0.015), versus 86% and 83%, respectively, after age 60 (p=0.89). G+/LVH− subjects had normal wall thicknesses, diastolic function and NT-proBNP levels, but subtle changes in LV geometry and more ECG abnormalities than their unaffected relatives.ConclusionsPhenotypic expression of the Icelandic MYBPC3 founder mutation varies by age, sex and proband status. Men are more likely to have LVH at a younger age, and disease manifestations were more prominent in probands than in relatives identified via family screening. G+/LVH− individuals had subtle clinical differences from unaffected relatives well into adulthood, indicating subclinical phenotypic expression of the pathogenic mutation.


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