his disorder is caused by a mutation in the cystic ibrosis conductance transmembrane regulator (CFTR) gene, which is located on the long arm of chromosome 7 and encodes a chloride-channel protein. Although the most common CFTR gene mutation associated with classic cystic fibrosis (CF) is the .F508 mutation, more than 2000 mutations have been identiied (Cystic Fibrosis Mutation Database, 2016). CF may develop from either homozygosiy or compound heterozygosiy for mutations in the CFTR gene. In other words, one mutation must be present in each copy of the gene, but they need not be the same mutation. As expected, this results in a tremendous range of clinical disease severity. Median survival is approximately 37 years, but approximately 15 percent have milder disease and can survive for decades longer. Care for the pregnant woman with CF is discussed in Chapter 51 (p. 998).
he American College of Obstetricians and Gynecologists (2017a,b) recommends that all patients who are considering pregnancy or who are already pregnant should be ofered carrier screening for CF, regardless of ethnicity. The current recommended screening panel contains 23 panethnic CF gene mutations, selected because they are present in at least 0.1 percent of patients with classic CF (American College of Obstetricians and Gynecologists, 20 17b). The CF carrier frequency approximates 1 in 25 in non-Hispanic white Americans and those of Ashkenazi Jewish descent, who are from Eastern Europe. Thus, the incidence of CF in a child born to a non-Hispanic white couple approximates 4 X 1/25 X 125, or 1 :2500. As shown in 1i4-11i, both CF incidence and the sensitivity of the screening test are lower for other ethnicities.
lthough a negative screening test result does not preclude the possibility of carrying a less-common mutation, it reduces the risk substantively from the background rate. If both parents are carriers, chorionic villus sampling or amniocentesis can help determine whether the fetus has inherited one or both of the parental mutations. Counseling following identification of two disease-causing mutations is challenging, because phenotype prediction is reasonably accurate only for pancreatic disease, and then only for well-characterized mutations. Prognosis is most heavily afected by the degree of pulmonary disease, which varies considerably even among individuals with the most common genotype associated with classic disease, that is, those homozygous for the .F508 mutation. his likely relects the efect of genetic modiiers on protein function, which may further vary depending on the CFTR mutation and on exposure and susceptibility to environmental factors (Cutting, 2005; Drumm, 2005).
his autosomal recessive disorder results in spinal cord motor neuron degeneration that leads to skeletal muscle atrophy and generalized weakness. here is currently no efective treatment. The prevalence of spinal muscular atrophy (SA) is 1 in 6,000 to 10,000 live births. Types I, II, III, and IV are caused by mutations in the survival motor neuron (SMN1) gene, which is
TABLE 14-1e1. Cystic Fibrosis Detection and Carrier Rates before and ater Testing
Ashkenazi Jewish 94.0 1/24 1 in 384 Caucasian 88.3 '1125 1 in 206 Hispanic American 71.7 1/58 1 in 203 African American 64.5 1/61 1 in 171 Asian American 48.9 1/94 1 in 183
Data from American College of Medical Genetics, 2006.