Biomedical subjects

Kerry Shooner

Publications and source records attributed to Kerry Shooner.

3 recordsLinked to original sources

PubMed2007

Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for bicuspid aortic valve and associated cardiovascular malformations.

The aim of this study was to identify regions of the genome that harbor genes influencing inheritance of bicuspid aortic valve (BAV) and/or associated cardiovascular malformation (CVM). Aortic valve disease is an important clinical problem, which often results in valve replacement, the second most common cardiac surgery in the United States. In every age group, a majority of cases of valve disease involves a BAV. BAV is the most common CVM with a reported prevalence of 1-2%. Heritability studies indicate that BAV determination is almost entirely genetic. We used a family-based genome-wide linkage analysis with microsatellite markers. Parametric and nonparametric analyses were performed with the software GENEHUNTER and SOLAR (Sequential Oligogenic Linkage Analysis Routines). Thirty-eight families (353 subjects) with BAV and/or associated CVM were assessed. Each participant underwent a standardized echocardiographic examination. The highest LOD score, 3.8, occurred on chromosome 18q between markers D18S68 and D18S1161. Two other chromosomal regions, 5q15-21 (between D5S644 and D5S2027) and 13q33-qter (between D13S1265 and 13qter), exhibited suggestive evidence of linkage (LOD > 2.0). Further, two previously reported linkage peaks on 9q34 and 17q24 were replicated in family specific analyses. No significant X chromosome linkage peaks were identified. In this genome-wide scan we demonstrate for the first time, that BAV and/or associated CVM exhibit linkage to chromosomes 18q, 5q and 13q. These regions likely contain genes whose mutation results in BAV and/or associated CVM indicating their important role in valvulogenesis and cardiac development.

Aortic Valve↗

PubMed2004

Bicuspid aortic valve is heritable.

OBJECTIVES: Previous studies have established familial clustering of bicuspid aortic valve (BAV), presumably indicating genetic inheritance. Our objective was to statistically test whether the segregation pattern of BAV is consistent with genetic inheritance and to obtain an estimate of the size of the genetic effect (heritability). BACKGROUND: Bicuspid aortic valve occurs in 1% of the population, making it the most common cardiovascular malformation (CVM). Bicuspid aortic valve is frequently an antecedent to aortic valve stenosis or insufficiency and is often associated with other CVMs, including aortic root dilation. The genetic and developmental significance of these findings remains obscure. METHODS: In 50 probands with BAV, we obtained a three-generation family history and echocardiograms on first-degree relatives. Heritability (h2) of BAV and BAV and/or other CVMs were estimated using maximum-likelihood-based variance decomposition extended to dichotomous traits implemented in the computer package Sequential Oligogenic Linkage Analysis Routines (SOLAR, San Antonio, Texas). RESULTS: A total of 309 probands and relatives participated. Bicuspid aortic valve was identified in 74 individuals (prevalence = 24%). A total of 97 individuals had BAV and/or other CVM (prevalence = 31%), including aortic coarctation, ventricular or atrial septal defect, abnormal mitral valve, aortic root dilation, or hypoplastic left heart syndrome. The heritability (h2) of BAV and BAV and/or other CVMs were 89% and 75%, respectively. CONCLUSIONS: The high heritability of BAV suggests that in this study population BAV determination is almost entirely genetic. The heritability of BAV plus other cardiovascular anomalies suggests that valve malformation can be primary to defective valvulogenesis or secondary to other elements of cardiogenesis.

Adolescent↗

PubMed2003

A candidate locus approach identifies a long QT syndrome gene mutation.

Long QT syndrome is an inherited disorder that results in lengthened cardiac repolarization. It can lead to sudden onset of torsades de pointes, ventricular fibrillation, and death. The authors obtained a family history, performed electrocardiograms, and drew blood for DNA extraction and genotyping from 15 family members representing 4 generations of an affected family. Seven individuals demonstrated prolonged QT intervals. The authors used polymorphic short tandem repeat markers at known LQTS loci, which indicated linkage to chromosome 11p15.5 where the potassium channel, KCNQ1, is encoded. Polymerase chain reaction was used to amplify the coding region of KCNQ1. During survey of the KCNQ1 coding region, a G-to-A transition (G502A) was identified. DNA from all clinically affected but from none of the clinically unaffected family members carried the G-to-A transition. The candidate locus approach allowed an efficient mechanism to uncover the potassium channel mutation causing LQTS in this family.

Adolescent↗