Researchers studying rare genetic disorders have uncovered insights into those diseases in biological structures that regulate chromosomes when cells divide. Focusing on the cohesin complex, a group of proteins forming a bracelet that encircles chromosome pairs, scientists have discovered mutations that disrupt cohesin, causing a recently recognized class of diseases called cohesinopathies.
"We are learning more about how these genetic abnormalities that affect cohesin play a role in human development," said study leader Matthew A. Deardorff, M.D., Ph.D., a specialist in pediatric genetics at The Children's Hospital of Philadelphia's Center for Cornelia deLange Syndrome and Related Diagnoses.
The research, carried out in children, cell cultures, and zebrafish, appeared May 24 in the American Journal of Human Genetics. Deardorff's co-study leader was Frank J. Kaiser, Ph.D., of the University of Lubeck in Germany.
The cohesin complex is already known to be involved in Cornelia deLange syndrome (CdLS), a multisystem genetic disease affecting an estimated 1 in 10,000 children. The disease has a range of severity, but classically includes mental retardation, impaired growth, heart defects, feeding problems, deformed arms and hands, and distinctive facial features.
Researchers at The Children's Hospital of Philadelphia previously were the first to discover gene mutations that cause CdLS, including forms of the disease with mental retardation and often severe limb abnormalities. The current study identified another gene, RAD21, that when mutated, causes very mild cognitive and physical impairments.
The study team first performed a genome-wide analysis of 101 children with typical CdLS and 189 children having overlapping features of the disease. None of the children had mutations in the three genes already known to cause CdLS. They identified a six-year-old boy with a deletion in a section of chromosome 8 that co
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Children's Hospital of Philadelphia