Imperial College London
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Rachel Buchan

Faculty of Medicine, National Heart & Lung Institute

Honorary Research Officer
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 88145rachel.buchan

 
 
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Location

 

2047Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Allouba:2020:10.1101/2020.03.24.20037358,
author = {Allouba, M and Aguib, Y and Walsh, R and Afify, A and Theotokis, P and Galal, A and Halawa, S and Shorbagy, S and Ibrahim, AM and Kassem, HS and Ellithy, A and Buchan, R and Hosny, M and Whiffin, N and Elguindy, A and Anwer, S and Cook, SA and Ware, JS and Barton, PJ and Yacoub, M},
doi = {10.1101/2020.03.24.20037358},
publisher = {Cold Spring Harbor Laboratory},
title = {Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity},
url = {http://dx.doi.org/10.1101/2020.03.24.20037358},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Hypertrophic Cardiomyopathy (HCM) is an inherited disease characterized by genetic and phenotypic heterogeneity. MYH7 represents one of the main sarcomere-encoding genes associated with HCM. Missense variants in this gene cause HCM through gain-of-function actions, whereby variants produce an abnormal activated protein which incorporates into the sarcomere as a "poison peptide". Here we report a frameshift variant in MYH7, c.5769delG, that is associated with HCM in an Egyptian cohort (3.3%) compared with ethnically-matched controls. This variant is absent from previously published large-scale Caucasian HCM cohorts. We further demonstrate strong evidence of co-segregation of c.5769delG with HCM in a large family (LOD score: 3.01). The predicted sequence of the variant MYH7 transcript shows that the frameshift results in a premature termination codon (PTC) downstream of the last exon-exon junction of the gene that is expected to escape nonsense-mediated decay (NMD). RNA sequencing of myocardial tissue obtained from a patient with the variant during surgical myectomy confirmed the expression of the variant MYH7 transcript. Our analysis reveals a new mechanism of pathogenicity in the understudied Egyptian population whereby distal PTC in MYH7 may lead to the expression of an abnormal protein.
AU  - Allouba,M
AU  - Aguib,Y
AU  - Walsh,R
AU  - Afify,A
AU  - Theotokis,P
AU  - Galal,A
AU  - Halawa,S
AU  - Shorbagy,S
AU  - Ibrahim,AM
AU  - Kassem,HS
AU  - Ellithy,A
AU  - Buchan,R
AU  - Hosny,M
AU  - Whiffin,N
AU  - Elguindy,A
AU  - Anwer,S
AU  - Cook,SA
AU  - Ware,JS
AU  - Barton,PJ
AU  - Yacoub,M
DO  - 10.1101/2020.03.24.20037358
PB  - Cold Spring Harbor Laboratory
PY  - 2020///
TI  - Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity
UR  - http://dx.doi.org/10.1101/2020.03.24.20037358
UR  - http://medrxiv/
UR  - http://hdl.handle.net/10044/1/82592
ER  -
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