Publications (5)4.24 Total impact
-
Article: Ebstein's anomaly may be caused by mutations in the sarcomere protein gene MYH7.
[show abstract] [hide abstract]
ABSTRACT: Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding β-myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members.Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 05/2011; · 1.44 Impact Factor -
Article: Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: a family study.
[show abstract] [hide abstract]
ABSTRACT: The endothelins are among the most potent vasoconstrictors known. Pharmacological inhibition of endothelin receptors lowers blood pressure (BP). It is unknown whether naturally occurring genetic variation in the endothelin receptors influences BP. We have evaluated the type A endothelin receptor (EDNRA) as a candidate gene for hypertension in a large family study. A total of 1425 members of 248 families selected via a proband with hypertension were studied. Ambulatory BP monitoring was conducted using the A&D TM2421 device. Four haplotype-tagging single nucleotide polymorphisms (SNPs) spanning the EDNRA gene were typed. There was evidence of association between genotype at the rs5335 (C+70G) SNP and night systolic blood pressure (+1.24% (s.e. 0.64) per G allele; P=0.05); night diastolic blood pressure (+1.64% (s.e. 0.71) per G allele; P=0.021) and night mean BP (+1.51% (s.e. 0.64) per G allele; P=0.017). Borderline significant trends in the same direction were seen for daytime BPs. Proportions of hypertensives in each of the three genotype groups were C/C 34.7%, C/G 37.9%, G/G 42.4% yielding an odds ratio for hypertension per G allele of 1.19 (95% confidence interval 1.00-1.41; P=0.05). In conclusion, the rs5335 (C+70G) polymorphism of the EDNRA gene has small effects on the risk of hypertension. Natural variation in other genes in the endothelin-signalling pathway should be explored to identify additional influences on BP regulation.Journal of Human Hypertension 04/2008; 22(4):282-8. · 2.80 Impact Factor -
Article: The C-532T polymorphism of the angiotensinogen (AGT) gene is associated with arterial stiffness: A possible explanation for heterogeneity in genetic association studies of AGT and hypertension
-
Article: The C-532T polymorphism of the angiotensinogen gene is associated with pulse pressure: A possible explanation for heterogeneity in genetic association studies of AGT and hypertension
-
Article: Mutations in the Sarcomere Protein Gene MYH7 in Ebstein's Anomaly
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND: -Ebstein's anomaly is a rare congenital heart malformation characterized by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. An association between Ebstein's anomaly with left ventricular noncompaction (LVNC) and mutations in MYH7 encoding beta-myosin heavy chain has been reported; here we have screened for MYH7 mutations in a cohort of probands with Ebstein's anomaly in a large population-based study. METHODS AND RESULTS: -Mutational analysis in a cohort of 141 unrelated probands with Ebstein's anomaly was performed by next generation sequencing and direct DNA sequencing of MYH7. Heterozygous mutations were identified in 8 of 141 samples (6%). Seven distinct mutations were found, 5 were novel and 2 were known to cause hypertrophic cardiomyopathy (HCM). All mutations except for one 3-bp deletion were missense mutations, one was a de novo change. Mutation-positive probands and family members showed various congenital heart malformations as well as LVNC. Among 8 mutation-positive probands, 6 had LVNC, whereas among 133 mutation-negative probands, none had LVNC. The frequency of MYH7 mutations was significantly different between probands with and without LVNC accompanying Ebstein's anomaly (p<0.0001). LVNC segregated with the MYH7 mutation in the pedigrees of three of the probands, one of which also included another individual with Ebstein's anomaly. CONCLUSIONS: -Ebstein's anomaly is a congenital heart malformation that is associated with mutations in MYH7. MYH7 mutations are predominantly found in Ebstein's anomaly associated with LVNC and may warrant genetic testing and family evaluation in this subset of patients.Circulation: Cardiovascular Genetics, v.4, 43-50 (2011).
Top Journals
Institutions
-
2008–2011
-
Newcastle University
Newcastle upon Tyne, ENG, United Kingdom
-