Biomedical subjects

Melodie R Winawer

Publications and source records attributed to Melodie R Winawer.

4 recordsLinked to original sources

PubMed2006

Phenotype definition in epilepsy.

Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

Epilepsy↗

PubMed2005

Genetic epidemiology of epilepsy or what do we tell families?

Over the past few decades, epidemiologic and molecular research has transformed the field of epilepsy genetics. In this review, we discuss the ways in which accumulating evidence on the genetics of epilepsy and febrile seizures can inform health care practitioners advising patients and families with epilepsy. We will review the epidemiologic data from twin and family studies, and illustrate how it can be used to guide genetic counseling. Although there have been many exciting advances in the last few decades-both molecular and epidemiologic-what we have learned has not appreciably changed what we tell families, and what we tell them can remain reassuring.

Adolescent↗

PubMed2002

Four new families with autosomal dominant partial epilepsy with auditory features: clinical description and linkage to chromosome 10q24.

PURPOSE: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. METHODS: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. RESULTS: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (theta=0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. CONCLUSIONS: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway.

Adult↗

PubMed2002

Epilepsy genetics.

BACKGROUND: Epilepsy genetics is a complex and rapidly expanding field that involves the contributions and collaborative efforts of geneticists, molecular biologists, epidemiologists, and clinicians. REVIEW SUMMARY: This article first provides a background review of basic terminology and contributions from the fields of epilepsy, genetics, and genetic epidemiology. It further describes the evidence for the genetic basis of epilepsy and enumerates the linkage findings and epilepsy susceptibility genes reported to date. It then addresses existing knowledge about the genetics of electroencephalogram abnormalities and their relationship to clinical epilepsy. Finally, it gives guidelines for genetic counseling, with attention to patients' frequently asked questions. CONCLUSIONS: This review provides a framework for understanding current and future investigations in the field of epilepsy genetics and a way to assist and educate individuals and families living with epilepsy.

Journal Article↗