Last week, Pathway launched its Extended Carrier Status Screening service, which examines prospective parents for 76 recessive genetic diseases. This newly extended service is available to physicians and their patients. In this week’s blog post, we focus on two diseases screened by this service: cystic fibrosis and homocystinuria, classic type.
Seventeen years ago, at 2 years old, Gunnar Esiason, the son of Boomer Esiason, NFL sportcaster and former Cincinnati Bengals quarterback, was diagnosed with cystic fibrosis. Shortly after his son’s diagnosis, Boomer founded the Boomer Esiason Foundation, a charity devoted to funding research for a cure for cystic fibrosis. Dramatically increasing the public awareness of cystic fibrosis, the foundation is also committed to further heightening public awareness of the condition, as well as educating and improving the quality of life for those who live with the disease.
Affecting over 70,000 people across the globe, cystic fibrosis is the most common genetic disease in Caucasians, and is caused by defects in the CFTR gene, which codes for a protein that transports electrolytes across cell membranes. Defects in the CFTR affect a person’s body in many ways, including the production of thick mucus in the lungs, blockage of digestive enzyme release in the pancreas, and blockage of sperm passage in the vas deferens. These physiological problems lead to the clinical symptoms of cystic fibrosis, which include chronic pulmonary disease, inflammation of the lower airways, gastrointestinal abnormalities, salt-loss syndromes, as well as infertility in males.
While there is currently no cure for cystic fibrosis, and death from complications of this condition is usually due to respiratory failure, prompt treatment to keep the lungs clear of thick mucus and to ensure adequate nutritional intake can help those with cystic fibrosis lead healthier and more productive lives. With such treatment, the average life expectancy of individuals with cystic fibrosis has increased to 37 years.
Pathway screens for more than 80 mutations in the CFTR gene, including all 23 mutations recommended for screening by the American College of Medical Genetics (ACMG) and by the American College of Obstetricians and Gynecologists (ACOG). Our screening includes the most recurrent mutation, known as deltaF508, which comprises up to 70 percent of cystic fibrosis mutations found in some populations, and is by far the most common CFTR mutation in the world. The availability of genetic screening for cystic fibrosis mutations, since the discovery of the CFTR gene in 1989, has resulted in a decreased incidence of the disease in several populations.
In Caucasians and Ashkenazi Jews, up to 1 in 25 people are carriers of a cystic fibrosis mutation. For Hispanics, African Americans and Asian Americans, 1 in 58, 1 in 61 and 1 in 94 people, respectively, are carriers of a cystic fibrosis mutation.
Homocystinuria, classic type
The characteristic physical features of individuals who suffer from the genetic disease called classic type homocystinuria have led researchers to speculate that the Egyptian Pharaoh Akhenaten, who became king in 1364 BC, suffered from homocystinuria. Since its discovery in 1962, classic type homocystinuria has become one of the state-mandated inborn errors of metabolism for which newborn infants are screened.
Classic type homocystinuria is a devastating disease in which affected individuals cannot break down particular amino acids (homocysteine and methionine) in the food they eat. These individuals have defects in the CBS gene, which codes for an enzyme called cystathionine beta-synthase. Newborns with homocystinuria usually do not have symptoms, and without newborn screening, the disease is often not diagnosed until after the age of 2 years. The first symptom is usually dislocation of the lens of the eyes. Other clinical symptoms may include skeletal abnormalities, such as scoliosis and long, thin arms and legs that give patients a Marfan-like appearance, as well as significantly impaired cognitive functioning, developmental delay and blood clotting problems.
If untreated, individuals with homocystinuria die at an earlier age than normal, usually from stroke or heart disease. However, if detected early, homocystinuria is treatable with a special diet and vitamin supplements.
Classic type homocystinuria is a rare disease so the carrier rate is not known. However, the worldwide incidence of the disease is estimated to be approximately 1 in 200,000 to 1 in 300,000 babies (with two copies of the bad gene). In some populations, the incidence is higher, with rates as high as 1 in 20,000 to 1 in 60,000 babies in Irish, German, Dutch and Australian populations. In comparison, consider that the incidence of cystic fibrosis is 1 in 2,500 to 3,000 babies (with two copies of the bad gene) in Caucasians.
How can extended carrier screening help?
Both cystic fibrosis and classic type homocystinuria are inherited in an autosomal recessive fashion. Each person has two copies of a gene, one from each parent, and both must be altered or mutated for a recessive disease to develop. People who are carriers have one good copy and one bad copy of the gene. Carriers are usually not affected and do not show any symptoms. If both parents are carriers, there is a 25 percent chance each child could inherit two copies of the bad gene and develop the disease.
For prospective parents, Pathway’s Extended Carrier Status Screening can tell them whether they are likely to carry one of the mutations that cause cystic fibrosis or classic type homocystinuria. If both prospective parents are positive for mutations in the same disease gene, their child can be screened for the disease as soon as he or she is born. If the child has the disease, treatment can begin immediately, and symptoms can be prevented. In some cases, parents choose assisted reproductive methods when a risk of a devastating disease is known, for example, people may elect to use preimplantation genetic diagnosis (PGD), egg or sperm donors, or other surrogacy methods to ensure that their child does not have the disease.