Medical Genetics - V. M. Zaporozhan 2005

Prevention of Hereditary Diseases
Identification of heterozygous carriers of recessive mutant genes as a method of primary prevention

Detection of heterozygous carriers of mutant genes can be performed: 1) in populations with a high incidence of a specific hereditary disorder; 2) in families at high risk for certain severe Hereditary diseases; 3) in couples entering consanguineous marriages.

1. Population screening for heterozygous carriers was first initiated among certain Ashkenazi Jewish populations, which have a high incidence of Tay-Sachs disease, or GM2 gangliosidosis (with a frequency of 1:3600 newborns). Screening for sickle-Cell trait (HbS) carriers is conducted in African-American populations in the USA and Cuba (frequency 1:600 newborns). In many Mediterranean countries and Cuba, screening for ß-thalassemia heterozygotes is carried out (frequency 1:3600 newborns in Italy, Greece, and Cyprus). Today, DNA diagnostic Methods are widely used for heterozygous carrier screening.

Heterozygote detection is also conducted among schoolchildren. All identified carriers are enrolled in the dispensary registry of the regional medical genetics counseling center. When marriage occurs between heterozygous carriers, the couple can undergo prenatal Diagnosis during each subsequent Pregnancy. Screening for heterozygous carriage has successfully reduced the incidence of ß-thalassemia in Cyprus and Cuba by more than 90 %.

Recently, screening to detect heterozygous carriers of the ΔF508 mutation in the cystic fibrosis Gene has been launched in England. This mutation accounts for at least 80 % of cystic fibrosis cases in the country, with the disease incidence approaching 1 in 2500 newborns.

In Ukraine, population screening for heterozygous carriage is not yet performed. It would likely be advisable to screen for heterozygous carriers of cystic fibrosis Gene Mutations, given that the incidence of this disease in certain regions reaches 1 in 1600 newborns, while the frequency of heterozygous carriers can be as high as 1:20.

2. Genetic testing to identify heterozygous carriage is widely practiced in families at high risk for certain severe hereditary diseases (such as cystic fibrosis, Duchenne muscular dystrophy, phenylketonuria, hemophilia, and many others). Individuals who require this testing are selected using the genealogical method. Of particular importance is the identification of female heterozygous carriers of recessive X-linked genes.

3. For couples who seek Genetic Counseling for reproductive risk assessment in consanguineous marriages, it is advisable to test for heterozygous carriage of common mutations in genes responsible for the most prevalent Monogenic Disorders (such as cystic fibrosis, phenylketonuria, spinal muscular atrophy, adrenogenital syndrome, etc.).