Cystic Fibrosis Screening: ALL Donors Screened for 86 mutations

Background 

Fairfax Cryobank continually strives to be the industry leader in genetic and infectious disease testing. We were the first Cryobank to provide genetic screening of all donors for Cystic Fibrosis (CF) starting in 1990.  Cystic fibrosis (CF) is the most common severe inherited disease in Caucasians. It is less frequent in individuals of Black or Asian ancestry. The disease usually begins in infancy or childhood with recurrent lung problems (including pneumonia), intestinal difficulties, or poor growth. Medications, frequent visits to physicians, and hospitalizations are almost always required. While there has been much improvement in the care of children with CF, many of them still die in early childhood, and about half of all individuals with CF die before they reach age 30.  Over 1000 different CF mutations within the CF gene have been identified to date. The most common, called Delta F508, accounts for 70% of all CF mutations, while many others have been seen in only a single family.

The American College of Medical Genetics (ACMG) in association with the American College of Gynecology and Obstetrics (ACOG) issued a position statement during 2001 stating that all Caucasian couples seeking pregnancy should be offered Cystic Fibrosis screening.  Click the link below to read the publication that this recommendation is based upon.

Laboratory Standards and Guidelines for Population-based Cystic Fibrosis Carrier Screening,Genetics in Medicine, March/April 2001, Vol. 3 No. 2: 149-154.

Just as Fairfax Cryobank was the first to screen ALL donors for Cystic Fibrosis back in 1990, Fairfax Cryobank is now the first to retroactively screen ALL donors on our register for 86 CF mutations including the 25 Cystic Fibrosis mutations in the ACOG/ACMG recommendation.  This means that every donor on our current donor register has been screened for 86 CF mutations.  Some sperm banks may be using a similar screening protocol on newly recruited donors, but please be sure to ask if all donors have been screened.  The risk of a Caucasian individual carrying a CF mutation is 1 in 29, and no screening currently available can eliminate all carriers from the population. Completion of screening for the 25 ACOG/ACMG recommended mutations decreases the possibility of a Caucasian individual being a carrier to 1 in 140. Screening donors for 86 mutations lowers the risk even further. The risk that a Fairfax Cryobank semen donor is a carrier of Cystic Fibrosis is lowered to 1 in 325.

Inheritance and Risks 

All couples have some risk of having a child with CF. Genes are passed to your child in the egg and sperm. Ordinarily you have two normal copies of a gene. If one copy of the CF gene is abnormal, you are still healthy, but are a carrier of CF. If you and your spouse are both carriers, you have a 1 in 4 chance that your baby will inherit two CF genes and be affected with CF. If this happens your child will have Cystic Fibrosis. Like most individuals, you may not realize that you may be at risk for having a child with the disease. Most CF carriers have no family history of affected family members. Approximately 1 in 29 Caucasian Americans are carriers of the CF gene. One in every 3,360 Caucasian births results in a child who is affected with Cystic Fibrosis. Individuals whose ancestors are African, Hispanic or Asian can also be affected with CF, but this occurs less often. For example, in the African American population, only one out of every 17,000 births result in a child who is affected with CF. 

Screening 

Until about 1990 you could not know whether you carried CF unless you had a child born with the disease. However, in 1989 the gene which causes CF was discovered and shortly thereafter a test that currently detects about 85% of all CF carriers was developed. Thus, a positive test diagnoses that you are a carrier, while a negative test greatly reduces, but does not eliminate, the risk of being a carrier.

Fairfax Cryobank screens all prospective donors for Cystic Fibrosis (1) by obtaining a detailed family medical history and (2) by performing genetic screening on a sample of the donor's blood. The specialized testing is performed by a fully licensed/accredited genetics laboratory. All Fairfax Cryobank donors have a negative test result for the 86 Cystic Fibrosis mutations screened.

At the present time, over 1000 different genetic changes (known as mutations) in the CF gene have been identified. Only one mutation is necessary to change a normal gene into a CF gene. The laboratory assays that are currently being used are designed to test for the most common mutations. Screening for all mutations is not practical since the majority of them are very rare and seen in only one family. At the present time Cystic Fibrosis carrier screening cannot provide 100% certainty that an individual is not a carrier of a CF mutation. DNA studies do not constitute a definitive diagnostic test or precise carrier test for CF in all families. Thus the interpretation of all data is usually given as a probability of being a carrier. 

Fairfax Cryobank recommends that the recipient of donor semen be screened to determine if she is a CF carrier (See Table 2). Current medical recommendations suggest a minimum of 25 mutations be screened.  If an individual receives a negative result for CF carrier screening, the chance of that person being a carrier of the CF gene is significantly reduced, although not completely eliminated.

Table


Likelihood Of Being a Cystic Fibrosis Carrier



Ethnic Background Before Testing
(no known family history)
After a negative
screening result
(using a 25 mutation screen)
Caucasian/  Non-Jewish 1/29 (4%) approx. 1/140
Ashkenazi Jewish 1/29 (4%) approx. 1/930
Hispanic 1/46 (2%) approx. 1/105
African  American 1/65 (1.4%) approx. 1/207

Table 2


  Fairfax Cryobank Donor Biological Father Carrier Status
Screened Negative for86 mutations Screened Negative for 25 mutations Unknown Known-Carrier
Biological MotherCarrier Status Unknown 1 in 37,700 1 in 16,240 1 in 3360 1 in 116
Screened Negative for 25 mutations 1 in 182,000 1 in 78,400 1 in 16, 240 1 in 560
Known-Carrier 1 in 1300 1 in 560 1 in 116 1 in 4