Exome Sequencing Helps Crack Rare Disease Diagnosis

Clinical analyses of patients’ gene sequences are helping to provide answers where none were available before.

Written byAmanda B. Keener
| 14 min read

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KATE WHITMOREOn a sunny day near Perth, Australia, two-year-old Scarlett Whitmore stares intently at her left shoulder. With absolute concentration, she raises her head to look at her physical therapist, who is holding onto Scarlett’s arm to keep her steady. “I’m so proud of you,” her mother, Kate Whitmore, cheers as she films the session with her camera phone. Looking proud herself, Scarlett rolls onto her back, stretches out her arms and legs, and smiles broadly. Her smile is infectious. Her green eyes grow wide whenever she flashes her toothy grin—the inspiration for “Scarlett’s Smile,” the name of the foundation her parents started to raise money for Scarlett’s medical expenses.

Scarlett has poor hearing and vision and hasn’t learned to sit up on her own, stand, walk, or speak. And for the first year of her life, her parents had no idea why. Just after Scarlett was born, “I remember my husband saying in the hospital, ‘She doesn’t cry,’ and I just said, ‘She’s a good baby,’” says Kate. After five months, however, Scarlett failed to meet typical milestones, such as making eye contact with her parents. And then the tests began. Full workups on her blood and spinal fluid didn’t suggest anything amiss. Neither did a test for large-scale chromosomal abnormalities. A viral screen revealed that Scarlett had been exposed to cytomegalovirus, a known cause of brain damage when contracted during development. But a ...

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