Company's Scientists also Enhance Industry Standards for Quality Screening
in Three Articles Published in The Journal of Molecular Diagnostics
MADISON, N.J., April 27 /PRNewswire-FirstCall/ -- Quest Diagnostics
scientists provide new insights into genetic factors affecting the accuracy
and quality of Cystic Fibrosis (CF) carrier and newborn screening in three
separate articles published in the May 2009 issue of The Journal of Molecular
Diagnostics. Quest Diagnostics Incorporated (NYSE: DGX) is the world's leading
provider of diagnostic testing, information and services.
The research may enhance the accuracy of carrier and newborn screening for
CF, a genetically inherited disease that damages the respiratory and
gastrointestinal systems. One in 29 Americans of Northern European Caucasian
or Ashkenazi Jewish descent are symptomless carriers of the defective, or
mutated, cystic fibrosis transmembrane regulator (CFTR) gene. A child whose
parents are both carriers has a one in four chance of developing the disease.
"Taken together, these three papers demonstrate how the widespread and
thoughtful experience with [cystic fibrosis] mutation testing and screening
continues to reveal new insights about the mutational alleles of the CFTR gene
and further refinements in how best to detect them and assure appropriate
quality control while doing so," said Wayne W. Grody, M.D., Ph.D., professor
in the Departments of Pathology and Laboratory Medicine, Pediatrics, and Human
Genetics at the UCLA School of Medicine. Dr. Grody, who wrote the commentary
"Cystic Fibrosis Testing Comes of Age(1)" in the journal's May issue, is not
affiliated with the studies.
"Since the CFTR gene was discovered two decades ago this year, scientists
have acquired significant insights into the genetics of CF, one of the most
common autosomal recessive genetic disorders," said Charles (Buck) Strom,
M.D., Ph.D., medical director of the genetic testing center of Quest
Diagnostics Nichols Institute, the esoteric research, development and testing
services operation of Quest Diagnostics. "As the world's leading provider of
genetic testing for cystic fibrosis, Quest Diagnostics has been at the
forefront of efforts to advance scientific understanding of the disease and
promote testing quality across the laboratory industry. These efforts are
noteworthy because insights into the more than 1,500 mutations affecting the
CFTR gene are enhancing the medical understanding of cystic fibrosis as well
as the mechanisms of other genetic diseases."
In "Apparent homozygosity of a novel frame shift mutation in the CFTR gene
because of a large deletion,(2)" Strom and his colleagues at Quest Diagnostics
present a patient with classic cystic fibrosis who exhibits previously
undescribed (novel) mutations that include deletions, or the absence, of large
parts of the CFTR gene. The investigators demonstrate that conventional
screening techniques may not accurately identify both defective CFTR genes in
patients who have inherited CFTR genes with large deletions. "The failure to
identify these CFTR mutations in carriers could increase the potential that
their family members are falsely identified as non-carriers," said Dr. Strom,
lead investigator of the study. "Comprehensive mutation analysis using DNA
sequencing and exon deletions/duplications is therefore important to resolve
apparent homozygosity (the false appearance that the patient inherited the
same mutations from each parent) for novel and rare mutations, some of which
are currently found in recommended testing panels."
In "Identification of cystic fibrosis (CF) variants by PCR/oligonucleotide
ligation (OLA) assay,(3)" Quest Diagnostics' scientists analyzed one million
specimens in the Quest Diagnostics database in order to identify rare genetic
variants that are potential sources of testing error. The investigators, led
by Victoria Pratt, Ph.D., FACMG, chief director, Molecular Genetics, Quest
Diagnostics Nichols Institute, identified eleven instances of "allele
drop-out," or failure to detect a targeted mutation, for an aberrancy rate of
less than 0.01%. "We concluded that the recognition and enumeration of such
variants along with clinical information in CF testing is valuable in avoiding
false-positive and false-negative results," Dr. Pratt said.
In addition, Quest Diagnostics, participated in a study coordinated by the
Centers for Disease Control and Prevention's Genetic Testing Reference
Material Coordination (GeT-RM) to develop a set of genomic DNA reference
materials for CF mutations not currently included in a 23-mutation test panel
recommended for carrier screening by the American College of Medical Genetics
(ACMG) and the American College of Obstetricians and Gynecologists (ACOG).
These additional mutations are currently offered in half of the nearly dozen
commercially available test panels on the CF testing market, which has grown
significantly since ACMG/ACOG made their first CFTR mutation screening
recommendation in 2001.
"Accurate characterization of CF mutations is essential to promoting
uniform standards and quality screening. Yet, the surge in CF testing demand
caused by ACMG/ACOG's promotion of broader population screening has outpaced
scientific efforts to characterize several mutations commonly found on test
panels used in clinical practice and research," said Dr. Pratt, investigator
of "Development of genomic reference materials for cystic fibrosis
testing.(4)" "The establishment of genomic DNA reference materials will
promote CF testing accuracy across the U.S. lab industry and may be expected
to advance CF research and development."
Quest Diagnostics and Genetic Screening
Quest Diagnostics is one of the leading providers of pre- and post-natal
and carrier genetic screening. In March 2009, the company announced that it
operates one of only three laboratories approved by the state of New York to
perform microarray-based comparative genomic hybridization (aCGH) postnatal
testing, using its ClariSure aCGH postnatal test, for copy-number chromosomal
abnormalities implicated in mental retardation, birth defects, and autism
spectrum and developmental disorders. The company also provides a broad-based
population screening technology designed to help determine whether parents are
carriers of the genetic mutation that causes Fragile X syndrome, the most
common form of inherited mental retardation. In 2002, the company launched its
CF Complete test, which enables physicians to identify rare mutations that
cause CF by sequencing the complete coding sequence of the cystic fibrosis
gene.
About Quest Diagnostics
Quest Diagnostics is the world's leading provider of diagnostic testing,
information and services that patients and doctors need to make better
healthcare decisions. The company offers the broadest access to diagnostic
testing services through its network of laboratories and patient service
centers, and provides interpretive consultation through its extensive medical
and scientific staff. Quest Diagnostics is a pioneer in developing innovative
diagnostic tests and advanced healthcare information technology solutions that
help improve patient care. Additional company information is available at
www.questdiagnostics.com.
(1) Grody W: Cystic fibrosis testing comes of age. J Mol Diagn 2009,
173-175
(2) Hanta FM, Reburying A, Pang M, Redman JOB, Sun W, Strom CM: Apparent
homozygosity of a novel frame shift mutation in the CFTR gene because of a
large deletion. J Mol Diagn 2009, 253-256
(3) Schwartz KM, Pike-Buchanan LL, Muralidharan K, Redman JB, Wilson JA,
Jarvis M, Cura MG, Pratt VM: Identification of cystic fibrosis (CF) variants
by PCR/oligonucleotide ligation (OLA) assay. J Mol Diagn 2009, 211-215
(4) Pratt VM, Caggana M, Bridges C, Buller AM, DiAntonio L, Highsmith WE,
Holtegaard LM, Muralidharan K, Rohlfs EM, Tarleton J, Toji L, Barker SD,
Kalman LV: Development of genomic reference materials for cystic fibrosis
testing. J Mol Diagn 2009, 186-193
SOURCE Quest Diagnostics
CONTACT: Media: Wendy Bost, +1-973-520-2800; Investors: Laure Park,
+1-973-520-2900
Web Site: http://www.questdiagnostics.com
(DGX)