Nav: Home

Ethnic differences in CF genetic coding not addressed in screening tests for nonwhite patients

December 16, 2015

Philadelphia, PA, December 16, 2015 - Cystic fibrosis (CF) occurs less frequently in nonwhites than in whites, and nonwhites tend to be diagnosed at a later age. This late diagnosis often comes only once they have become symptomatic, rather than through newborn screening programs or molecular diagnostic testing. Delaying diagnosis can result in postponed treatment and clinical deterioration. A new study in The Journal of Molecular Diagnostics found that one reason for this ethnic disparity in CF diagnoses is that the variants examined in the most common CF newborn screening panels do not sufficiently include the variants present in nonwhite populations.

"We think that this information can be used to optimize newborn screening programs, taking into account the ethnic composition of state populations, resulting in earlier diagnosis and intervention, timely clinical treatment, and enhanced prognosis," explained Iris Schrijver, MD, professor of pathology and, by courtesy, of pediatrics at the Stanford University School of Medicine, and director of the Stanford Molecular Genetic Pathology Service, Stanford, CA. "We believe it could propel equity in mutation detection for white and nonwhite CF patients."

As part of the study at Stanford University, the investigators examined CFTR genotyping of CF individuals in the CF Foundation Patient Registry across different racial and ethnic groups, including non-Hispanic whites (22,206), Hispanics (1,955), blacks (1,214), Asians (156), and Native Americans (171).

Mutations in the 27-exon CFTR gene that encodes the CF transmembrane conductance regulator (CFTR) underlie CF. Disruption of CFTR production and/or function affects chloride ion channels and thus interferes with the transport of electrolytes. This defective ion transport in the respiratory tract leads to less airway surface liquid and the formation of thick and sticky airway secretions that block lung passages. Individuals with CF may also have higher than normal levels of salt in their sweat.

The researchers found that 90% of white patients and 83% of Native Americans with CF have a particular mutation (p.Phe508del), and about half of these individuals have two copies of these mutations. However, they found that 30% of Hispanics, 38% of blacks, and 41% of Asians did not even have one copy of the mutation. Patients of Hispanic, black, or Asian ancestry were also less likely to have two identified CFTR variants. "Our results confirm the widely held notion that the American College of Medical Genetics and Genomics list of 23 mutations that was specifically designed for carrier screening is inadequate for diagnostic testing, even though it is used widely," commented Dr. Schrijver.

When the investigators compared Registry results from 2008 to 2013, they documented that genetic analyses were reaching greater proportions of CF individuals. For instance, in 2008 21% of whites were not yet genotyped compared to 9% in 2013. Although similar trends were observed across all ethnic groups, significantly greater proportions of individuals in nonwhite ethnic groups remained not yet genotyped compared to whites (eg, 19% of blacks versus 9% of whites).

To learn more about the spectrum of CTFR variants in nonwhite individuals, the investigators used direct DNA sequencing to study 140 individuals in the Registry. They found that 89 had two CFTR variants, including seven novel ones. Multiplex ligation-dependent probe amplification (MLPA) detected 14 rearrangements in the remaining 51 patients, six of which had not been described before. Because the investigators found that deletions and duplications were relatively common in the nonwhite CF patients, yet many were not previously reported, they suggest that testing should be expanded to include MLPA analysis.

CF, an inherited life-threatening disorder, affects the exocrine epithelial cells of multiple tissues and organs. Serious pulmonary problems occur, including chronic lung infections and airway inflammation. Other symptoms include failure to thrive, pancreatic insufficiency, infertility, and bowel obstruction. Its prevalence is approximately 1:2500 in whites, 1:15,000 in blacks, 1:35,000 in Asians, and 1:10,900 in Native Americans.
-end-


Elsevier Health Sciences

Related Native Americans Articles:

Latin-Americans with different Native-American ancestry show different health risks
Latin-Americans originate from a mix of people with Native-American, European and African ancestry.
MU professor first in nation to develop medical curriculum tailored to Native Americans
Melissa Lewis, Ph.D., assistant professor in the Department of Family Medicine at the MU School of Medicine, led the first project in the nation to develop a mandatory medical school curriculum about indigenous health.
Wheat virus crosses over, harms native grasses
Once upon a time, it was thought that crop diseases affected only crops.
FSU researchers talk turkey: Native Americans raised classic holiday bird
Researchers found turkeys were being raised and managed by Native Americans years before the first Thanksgiving.
Non-native insects change more than native host plant survival
Leaf litter chemistry of Guam's native cycad examined to determine the effects on soil chemistry.
Climate change may benefit native oysters, but there's a catch
Climate change may actually benefit oysters in California in the long term because they grow faster at warmer temperatures and are tolerant of extreme temperatures.
Researchers produce first major database of non-native English
After thousands of hours of work, MIT researchers have released the first major database of fully annotated English sentences written by non-native speakers.
OU center examines how genomic information impacts medical care of Native Americans
A University of Oklahoma Center on American Indian and Alaska Native Genomic Research will examine the impact of genomic information on American Indian and Alaska Native communities and health care systems.
Seeing isn't required to gesture like a native speaker
People the world over gesture when they talk, and they tend to gesture in certain ways depending on the language they speak.
Invasive water frogs too dominant for native species
In the past two decades, water frogs have spread rapidly in Central Europe.

Related Native Americans Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...