Jackie Smith’s Journey To Diagnosis

Our partner Claritas Genomics, who together with Boston Children’s Hospital use WuXi NextCODE’s integrated genome testing and research system, describe one woman’s journey to diagnosis

Some 7,500 rare disorders are known to be caused by single gene mutations. A vast majority of these disorders first appear at birth or in early childhood. For half of these conditions, the responsible gene has been identified. Yet the family of a child with one of these disorders spends an average of 12 years searching before finding a correct diagnosis.

Jackie Smith, who today is a 35-year-old mother of two, spent 32 years searching for the cause of her muscular weakness. Jackie’s parents knew something was wrong when she was born. They thought it might be bow-leggedness, because her ankles were turned in. At three, Jackie had a muscle biopsy taken and received a diagnosis based upon that biopsy of centronuclear myopathy.

Because gene discovery for muscle conditions is a recent development, many healthcare providers still do not recommend gene testing for their patients with these rare disorders. “The typical advice to parents is a genetic diagnosis doesn’t matter if there is no current treatment or cure,” says Anne Rutkowski, M.D, director of CMDIR, the Congenital Muscle Disease International Registry. The CMDIR is the largest database of both genetically confirmed and unconfirmed individuals with congenital muscle disease.

Jackie and her family were told that her condition would not progress, but this conflicted with Jackie’s own experience as she grew weaker in her teens. Today, Jackie is in a wheel chair. Like many people with muscular disorders, Jackie finally gave up on finding a diagnosis, going for medical care only for help with her symptoms.

Jackie heard about CMDIR when she was doing online research into congenital myopathies and says they opened her eyes to genetic testing.

In early 2015, Anne Rutkowski suggested she try one more time, with Claritas Genomics’ Pediatric Neurology Exome, a new test in development. Anne had been following Claritas’ new approach to genetic testing.

Claritas’ Pediatric Neurology Exome, developed in collaboration with experts from Boston Children’s Hospital, is a comprehensive, whole exome-based assay that uses an innovative orthogonal approach in which two separate and independent processing methods capture and sequence the exome and focus interpretation on 614 genes related to neurological disease, with a first set of results in 3-4 weeks. Claritas’ gene tests, like the Neurology Exome, are the first step in a process to help patients like Jackie in their search for answers. Claritas has established a framework of disease experts, technologies and gene databases that make the best genetic information and expertise available in one place, so that patients can receive the best possible diagnoses to inform and guide their care in weeks or months instead of years.

Jackie approached Claritas, where she became the first person to be screened with the firm’s new Pediatric Neurology Exome. After receiving her biological specimen, her results arrived three weeks later. That is when Jackie learned that her centronuclear myopathy is caused by two rare variations in the same gene, RYR1.

There is no treatment yet for centronuclear myopathy. A disappointment for Jackie and her family. But, when asked how she felt about knowing that a gene called RYR1 is the cause of her condition, Jackie said that it has made a world of difference:

Knowing [my gene variations] for me has been about information. I found out how it could affect my children. I now know my girls are carriers, and all of us can plan for the future better. It’s important for me that they can make informed choices. They’ve seen what I’ve gone through and that will help them with their family planning.

Jackie has begun corresponding with other people with the same RYR1 variations. This has given her a community she did not have before. For the first time, Jackie can converse with people who know exactly what she is going through.

Claritas facilitates access to research opportunities for patients who have taken their tests, so that anyone who wants to contribute to future rare disease discoveries can. Jackie has enrolled in a congenital myopathy study run by Dr. Alan Beggs, a professor of pediatrics at Harvard Medical School and the Director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital. Beggs has been collecting genetic data from patients and their families since the 1990s, searching for the gene variations responsible for congenital myopathies.

Claritas’ Pediatric Neurology Exome has allowed us to leapfrog past the genetic testing stage to identify patients with mutations in particular genes that we can now study further to develop treatments,” says Beggs. “Without Claritas’ Pediatric Neurology Exome, it might have taken us a year or longer to identify the RYR1 gene. Their ability to do so in three weeks frees us up to spend more time studying that muscle and creating that mutation in a zebra fish or a mouse so that we can use it to develop new treatments.

An added benefit, Beggs says, is that the Neurology Exome’s results can be used to help treat patients because Claritas’ laboratory is CLIA-certified, while his research studies are not. Claritas is also working with the Manton Center to develop tests that address anybody with an orphan disease.

Patrice Milos, PhD, Claritas Genomics president and CEO says that Jackie’s story illustrates the urgent need to make genetic testing a standard part of patient care. “We believe that now is the time to integrate gene testing into clinical practice,” she stated. “Our mission at Claritas, in partnership with Boston Children’s Hospital and others, is to make that happen by expanding the rate of diagnosis, improving tests and technology use, and by making information and expertise available to healthcare providers no matter how remote their location.”

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A three-decade diagnostic odyssey ended in three weeks - one woman’s journey to diagnosis.

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Through Claritas’s partnership with
WuXi NextCODE, we are able to offer patients and their healthcare providers the most powerful diagnostic capabilities available at remarkable speed, running Claritas’s test data through WuXi NextCODE’s population-scale genetic database. This large scale is especially important to successfully identify medically-relevant genetic variations and support our diagnosis for patients, like Jackie, who may have a rare disease.
Patrice Milos, PhD; President and CEO, Claritas Genomics