Linda Crnic Institute Lectures: “Trisomy 21: Causes and Consequences”

Stephanie Lee Sherman, PhD

Professor of Epidemiology and Human Genetics, Emory University
January 4, 2012

Click here to watch Dr. Sherman’s presentation

Dr. Sherman’s research program revolves around two syndromes that are related by their phenotype consequence, intellectual and development disabilities (IDD), but not their genetic etiology. These two syndromes include Down syndrome and fragile X syndrome. For both, Dr. Sherman uses genetic epidemiological approaches to answer questions related to the underlying genetic mechanism leading to the syndrome and the resulting phenotype consequences.

 Over 95% of cases with Down syndrome are caused by the abnormal segregation of chromosome 21 during the formation of eggs and sperm. This syndrome is the most common identified cause of IDD in humans and a major cause of miscarriages in older women, limiting their reproductive life span. In addition to IDD, individuals with Down syndrome have characteristic medical findings that significantly jeopardize their health and survival, including congenital heart defects, gut abnormalities and leukemia. Dr. Sherman and her colleagues have completed two large population-based study of Down syndrome live births and their parents and have combined cytogenetic, molecular and epidemiological tools to elucidate the cause of this chromosome error and its clinical consequences (Atlanta Down Syndrome Project (ADSP); National Down Syndrome Project (NDSP)).

In addition, Dr. Sherman also collaborates with several sites in a research program to identify genes and/or environmental exposures that lead to the susceptibility of birth defects, specifically those that occur in high frequency among individuals with Down syndrome relative to the general population. This large undertaking will potentially identify new strategies of clinical intervention and/or prevention. 

Fragile X syndrome, a type of inherited IDD, is part of a group of disorders known as fragile X-associated disorders. These are related to one another by the expansion of an unstable CGG repeat sequence located in the 5’ untranslated region of the FMR1 X-linked gene. The full mutation (>200 methylated repeats) leads to fragile X syndrome. The premutation (55-199 unmethylated repeats) leads to an increased risk for a late-onset tremor/ataxia syndrome (FXTAS) and, among women, primary ovarian insufficiency (FXPOI). We have established a large genetic epidemiological study of non-clinically referred individuals with high repeat tracts to study the neurological and neuropsychological consequence of these alleles. For females, we also study hormone levels and reproductive histories to better understand factors related to the risk of POI. Our goal is to understand the environmental and genetic factors that increase the risk and severity of both FXPOI and FXTAS. Importantly, in collaboration with Dr. Jeannie Visootsak, the clinical director of the Emory Fragile X Center, we work to translate our findings to families with fragile X associated disorders.

Dr. Sherman has a B.S. from North Carolina State University, and a Ph.D. in Human Genetics from Indiana University Medical School.