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Discovery of Susceptibility Gene Leads to a Family’s New Start

The 46 human chromosomes are shown in blue, with the telomeres appearing as white pinpoints. (Photo credit: Hesed Padilla-Nash and Thomas Ried)

Over the past 14 years, researchers in the Clinical Genetics Branch (CGB), led by Branch Chief Sharon Savage, M.D., have carried out a study of dyskeratosis congenita (DC) at the NIH Clinical Center to better understand the disorder and to identify the genes responsible for it.

DC is a rare inherited bone marrow failure and cancer predisposition syndrome caused by aberrant telomere biology. Telomeres are specialized structures at the ends of chromosomes that are essential for maintaining chromosomal integrity. DC is often diagnosed in early childhood but individuals can develop features of DC at any age. Families who have one child with DC are at high risk for having future children with the disorder.

Using exome sequencing, Dr. Savage and her team have identified several genes that cause DC, including RTEL1, a gene known to be involved in telomere biology. Discovery of a rare founder mutation in this gene has led to a direct benefit for at least one DC family. The story has been covered in the popular press. Read more about it here.

“Next generation platforms for genetic studies have accelerated our progress and allowed us to identify additional DC genes in record time,” Dr. Savage said. “This family’s triumph was the result of successful exome sequencing studies. It’s truly gratifying to hear of such a success story.”

Dr. Savage is actively engaged in a number of other studies of telomere biology, and its contribution to cancer etiology. Read more about telomere biology disorders.