Title: Genetic Modifiers of the Cardiac and Palate Phenotypes in 22q11.2 Deletion Syndrome
Stephanie Ciosek
Fall 2009
ABSTRACT:
BACKGROUND: The phenotype observed in individuals with a deletion of the 22q11.2
chromosomal region is highly variable, with no real understanding of the source of this variation.
Approximately 75% of cases have a cardiac defect, and up to 69% show a palate malformation,
with the severity ranging from mild to severe. The genes deleted in this region do not fully
explain the range of phenotypes or severity observed. METHODS: Families in whom the deletion
was inherited were identified through the 22q and You Clinic at Children’s Hospital of
Philadelphia. DNA was collected from 75 family members and used in a genome-wide
association study to investigate potential genetic modifiers of the cardiac and palate
phenotypes. Family-based association tests were used to compare genotypes at cardiac and
palate development genes between those with and without malformations. The chi-square test
was used to compare genotypes in the deleted region on the non-deleted chromosome.
RESULTS: Analysis is ongoing and is expected to be complete later this winter. CONCLUSIONS:
We hope to find genes that modify the phenotype seen with cardiac and palate malformations,
and then extend our methodology to investigate modifiers of the other phenotypes associated
with the 22q11.2 deletion syndrome. We also discuss the implications for genetic and newborn
screening.