Luke, I assume Mary is your wife? I would love to hear what her prof. has to say about this topic. I have never heard of this situation, the whole, two on one chromosome, one on two chromosomes, two on two different chromosomes.... It really doesn't make any sense to me at this point. Maybe she can shed some light. All I can draw from this is that if someone has CF symptoms, whether they be digestive, lung, or infertility (CBAVD/CAVD), or any combination of the three and they are in a situation like this (two mutations on one chromosome, or two chromosomes) and it needs to be treated like CF, they why not call it CF. I just really don't understand. If they have no signs or symptoms, then yes, I do understand, but like Mason's mom said that her husband and son have symptoms, mainly digestive. If you have to treat that like you would someone with CF, then I would have to conclude that they DO indeed have CF. I guess this is just one topic I have NO answers or even recommendations to.
As for the different labs, genzyme only tests for 86 mutations so they aren't all that much better or more reliable than a local lab that would test for 25 mutations. Here's some information I found on HollyCatheryn's website:
<i>Currently available DNA tests cannot identify all CF gene mutations. At present, diagnostic DNA tests screen for between 6 and 72 CF mutations. Available genetic tests are optimized for detecting the gene mutations such as deltaF508 that are most common among Caucasians. In other population groups, therefore, these tests are much less sensitive. These tests can identify 90% of the cases occurring in Caucasians but only 75%, 57%, and 30% among persons of African, Hispanic, and Asian decent, respectively. </i>
<i>Since 1991, genetic counseling with testing for the most common CF mutations has been offered to all presumptive fathers [at our center]. One expectant father was found to be a carrier for the R117H mutation. The couple decided to continue the pregnancy and declined further prenatal investigation of the fetus. The child did not inherit the mutation. One infant had CF diagnosed, despite having no mutations found on a previous genetic screening of the father that had been performed elsewhere.</i>
<i>As of 1999) over 800 mutations in the CFTR gene have been identified, although not all are disease causing. The most common mutation in the UK is the three base pair deletion, deltaF508, which accounts for 75% of carriers; three commercial multiple-mutation assays are available that can detect about 86% of carriers in Scotland, Wales and the North of England, or 80% elsewhere. Different proportions apply to Asians (35%), Ashkenazi Jews (95%) and Blacks (41%). </i>
<i>The UK birth prevalence is 1 in 2400, which implies a carrier frequency of 1 in 24. A carrier couple have a one in four risk that each of their children has CF; this is reduced to under one in 50,000 if neither parent has a detectable mutation. When only one parent is a carrier the risk is about 1 in 500. </i>
<i>Usually probands are told that close relatives can be screened but only one-third of first- and one-tenth of second-degree relatives are tested. There have been three studies of the more active cascade screening approach. Uptake was higher and a large proportion of those tested were carriers. However, mathematical models have shown that under 15% of carriers in the population would be detectable this way.</i>
<i>Carrier screening of the general population is possible using DNA mutation analysis. CF carrier testing is not recommended at this time (2003) unless a family history of CF is present. It is difficult to detect all carriers. Only 80 - 90 percent of carriers will be identified with the available tests. Newborn screening is recommended to prevent malnutrition as well as improve lung condition.</i>
<i>Cystic fibrosis is an autosomal recessive disease with a carrier rate of 1 in 22 to 25 in Caucasian Americans of Northern European background; the most common mutation in this group is called F508 (accounting for 75 percent of disease).The CF gene is also common among individuals of Ashkenazi Jewish heritage, who have a carrier rate of 1 in 25. The most common mutations in this latter population are 5T and W1 2828 (accounting for 48 percent of cases). The identity of the most common mutations in other racial or ethnic groups is not completely known (2001).</i>
<i>[There are] more than 1,000 mutations of the CF gene [as of 2004].</i>
Julie (wife to Mark 24 W/CF)
As for the different labs, genzyme only tests for 86 mutations so they aren't all that much better or more reliable than a local lab that would test for 25 mutations. Here's some information I found on HollyCatheryn's website:
<i>Currently available DNA tests cannot identify all CF gene mutations. At present, diagnostic DNA tests screen for between 6 and 72 CF mutations. Available genetic tests are optimized for detecting the gene mutations such as deltaF508 that are most common among Caucasians. In other population groups, therefore, these tests are much less sensitive. These tests can identify 90% of the cases occurring in Caucasians but only 75%, 57%, and 30% among persons of African, Hispanic, and Asian decent, respectively. </i>
<i>Since 1991, genetic counseling with testing for the most common CF mutations has been offered to all presumptive fathers [at our center]. One expectant father was found to be a carrier for the R117H mutation. The couple decided to continue the pregnancy and declined further prenatal investigation of the fetus. The child did not inherit the mutation. One infant had CF diagnosed, despite having no mutations found on a previous genetic screening of the father that had been performed elsewhere.</i>
<i>As of 1999) over 800 mutations in the CFTR gene have been identified, although not all are disease causing. The most common mutation in the UK is the three base pair deletion, deltaF508, which accounts for 75% of carriers; three commercial multiple-mutation assays are available that can detect about 86% of carriers in Scotland, Wales and the North of England, or 80% elsewhere. Different proportions apply to Asians (35%), Ashkenazi Jews (95%) and Blacks (41%). </i>
<i>The UK birth prevalence is 1 in 2400, which implies a carrier frequency of 1 in 24. A carrier couple have a one in four risk that each of their children has CF; this is reduced to under one in 50,000 if neither parent has a detectable mutation. When only one parent is a carrier the risk is about 1 in 500. </i>
<i>Usually probands are told that close relatives can be screened but only one-third of first- and one-tenth of second-degree relatives are tested. There have been three studies of the more active cascade screening approach. Uptake was higher and a large proportion of those tested were carriers. However, mathematical models have shown that under 15% of carriers in the population would be detectable this way.</i>
<i>Carrier screening of the general population is possible using DNA mutation analysis. CF carrier testing is not recommended at this time (2003) unless a family history of CF is present. It is difficult to detect all carriers. Only 80 - 90 percent of carriers will be identified with the available tests. Newborn screening is recommended to prevent malnutrition as well as improve lung condition.</i>
<i>Cystic fibrosis is an autosomal recessive disease with a carrier rate of 1 in 22 to 25 in Caucasian Americans of Northern European background; the most common mutation in this group is called F508 (accounting for 75 percent of disease).The CF gene is also common among individuals of Ashkenazi Jewish heritage, who have a carrier rate of 1 in 25. The most common mutations in this latter population are 5T and W1 2828 (accounting for 48 percent of cases). The identity of the most common mutations in other racial or ethnic groups is not completely known (2001).</i>
<i>[There are] more than 1,000 mutations of the CF gene [as of 2004].</i>
Julie (wife to Mark 24 W/CF)