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 recognised class of diseases called cohesinopathies. "We are learning more about how these genetic abnormalities that affect cohesin play a role in human development," said Doctor Matthew A. Deardorff.
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 contains the RAD21 gene, which was known to express a cohesin protein but not previously known to cause disease. As an infant, the boy had been diagnosed with facial features similar to those of CdLS, and subsequently experienced growth retardation, but had normal cognitive development.
The researchers then focused on three additional children with deletions in RAD21 and two children with mutations within the gene, and found a similar pattern—physical features, such as short stature and distinctive facial features, overlapping with some of those seen in cohesin disorders, but with only minor cognitive delays. "These findings suggest that children who are very mildly affected may go undiagnosed," said Deardorff.
MEDICA.de; Source: Children's Hospital of Philadelphia