Cystic Fibrosis


BACKGROUND:

Cystic fibrosis (CF) is an autosomal recessive disorder generally characterized by chronic obstructive lung disease, pancreatic insufficiency, poor gastrointestinal tract absorption and elevated sweat electrolytes. Other manifestations of CF have now been recognized to include male infertility caused by bilateral absence of the vas deferens, recurrent nasal polyps, rectal prolapse and chronic bronchiectases. The incidence of CF varies widely among different ethnic and racial groups, (from 1:3300 live births in those of Northern European descent, 1:6400 for Southern European groups, 1:8500 for American Hispanics, 1:17,000 for African-Americans, to being extremely rare in Asian populations).

Recommendations by an independent Consensus Panel convened by the NIH on genetic testing for CF (released on April 16, 1997) are the following:

  1. Offer testing for common gene mutations that cause CF as an option to all pregnant couples and those planning pregnancy. (Although more than 600 CF mutations have been identified, the vast majority are rare, so expanding the panel of screened mutation beyond the common mutations referred to above is expected to achieve only marginal gains in sensitivity.)

  2. Offer testing to individuals with a family history of disease and partners of people with CF.

  3. Insurance should cover the procedure in all of these populations.

INDICATIONS FOR TESTING:

  • All pregnant couples and couples planning pregnancy.

  • Confirmation of a clinical diagnosis of CF.

  • Carrier testing for those with a family history of CF.

  • Prenatal testing for known carrier couples.

  • Carrier screening in the Ashkenazi Jewish population.

  • Prenatal testing where ultrasound indicates echogenic bowel, obstructed bowel or fetal meconium ileus.

  • Diagnosis for individuals with bilateral absence of the vas deferens.

SAMPLE REQUIREMENTS:

Blood: Two 5 ml purple top (EDTA) vacutainers of whole blood inverted several times to mix. Forward within 48 hours at room temperature.

Amniotic Fluid: 10-15 ml amniotic fluid from 14th-17th week of gestation or one confluent flask of cultured cells. Send specimen refrigerated, but not frozen (do not ship on dry ice). Please use an overnight courier service.

INTERPRETATION:

PCR based assays are used to detect 70 common CF mutations 

Report will include assay results, background information, and a calculation of residual carrier risk if results are negative.

Results will take approximately one week.

COUNSELING ISSUES:

  1. The absence of a detectible CF mutation does not exclude a diagnosis of CF or CF carrier status. Over 600 CF mutations have been discovered, the vast majority being rare and seen only in individual families. The following table depicts the frequency of detectible mutations in various population groups as well as the overall carrier frequency in these groups.


    Racial or Ethnic Group

    Detection Rate

    Carrier Rate prior to testing

    Carrier risk after Negative test result

    Ashkenazi Jewish

    94%

    1/24

    Approximately 1/400

    Non-Hispanic Caucasian

    88%

    1/25

    Approximately 1/208

    Hispanic American

    72%

    1/46

    Approximately 1/164

    African American

    65%

    1/65

    Approximately 1/186

    Asian American

    49%

    1/94

    Approximately 1/184

  2. For family/carrier testing, it is most helpful to analyze an affected individual or their obligate carrier parents as a prelude to testing other at-risk members within the family.
  3. When mutations are not detected by direct DNA testing, linkage analysis may be a useful alternative for that family. Consultation with the laboratory director may be helpful.
  4. Genetic counseling is indicated to help individuals understand the implications of both positive and negative test results or in situations where the clinical diagnosis is uncertain or atypical.

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