Quest Diagnostics recently announced findings from several research projects detailing the clinical value of genetic tests to help predict or detect diseases. Data from the studies, which are being presented at the 2015 American Society of Human Genetics (ASHG) Annual Meeting being held Baltimore, Maryland from October 8-10, 2015, show that screening for genetic mutations above what is recommended in medical guidelines may help parents identify the risk of having a child with cystic fibrosis (CF). Other results suggested that a novel diagnostic technique based on “molecular combing” may be a potential game changer in genetic testing and help diagnose diseases like facioscapulohumeral dystrophy (FSHD).
Cystic fibrosis is characterized by progressive damage to the respiratory and gastrointestinal systems due to mucus buildup. In the US, an average of 30,000 individuals are affected and one individual in 29 is considered a carrier of the disease. Patients with CF may suffer from repeated lung infections, cough, slow growth, fatty stools, and infertility among others. There is no cure for CF, but the disease can be managed by various medications to relieve the symptoms and slow the disease from progressing. On the other hand, facioscapulohumeral dystrophy is a muscle weakening disease that initially affects the skeletal muscles of the face and upper arms. The prevalence of FSHD is regional, but a population based study revealed an average of 4 to 12 cases for 100,000 individuals are affected with the disease. Patients with FSHD suffer from facial muscle and shoulder weakness, hearing loss, loss of strength in abdominal muscles and foot drop, among others.
Both CF and FSHD are mostly caused by genetic mutations, of which several mutating genes have been identified while others have not yet been discovered. It is well known that mutations yield different defects that are responsible for disease severity. As a result, if all the mutations were identified, it could lead to better diagnostic solutions for patients. Quest Diagnostics has developed a vigorous research program on genetics focused on advancing the clinical value of laboratory diagnostics.
With regard to CF, in order to help identify carrier status in children, previous studies based on ACOG/ACMG evaluation dating back to 2004 recommended that physicians offer test panels based on 23 mutations of the CTFR gene, which is known to cause CF. Studies conducted at Quest Diagnostics detected pathogenic CFTR mutations, of which 18% did not belong to the recommended 23-gene panel. In 2010, Quest Diagnostics found that testing for CTFR genetic mutations beyond the recommended 23 mutations may help detect mutations of mild disease, but would unlikely prevent children from being born with classic CF. As a result, commercial and research laboratories have adopted the concept of next generation sequencing with the purpose to screen out for more genetic data that would improve detection of disease risk. The latter led to identification of a large percentage of CTFR mutations that would have otherwise been missed.
Other data to be presented at the ASHG Annual Meeting will deal with FSHD, where Quest Diagnostics investigators identified certain genomic characteristics of the disease using a novel technique called molecular combining. This tool, which is based on visualization of DNA fibers, allows detection of abnormalities that other techniques miss. It is worth noting that currently utilized diagnostic tools for FSHD yields inconclusive results in up to 23% of cases. However, by using a “molecular combing” technique, the scientists were able to determine the genetic carriers that differentiate FSHD patients from non-FSHD. Furthermore, a correlation between average age of individuals and specific genetic carriers was observed. This means that predicting the age of FSHD onset could help in life planning decisions.
In conclusion, Quest Diagnostics results suggest the need for a revision of the current practice guidelines for genetic testing to identify CF carrier risk by performing more genetic screenings. On the other hand, the novel molecular combing technique could be a potential game changer in genetic testing and additional research could lead to efficient diagnostic of FSHD and other inherited diseases like breast and ovarian cancers. Other presentations from Quest Diagnostics dealing with other genetic issues are being presented during this ASHG Annual Meeting.