Medical Genetics - V. M. Zaporozhan 2005

Prevention of Hereditary Diseases
Identification of genes associated with late-onset hereditary diseases and predisposition genes for multifactorial disorders, alongside the prevention of such pathologies in gene carriers

A promising direction in preventive care is the identification of genes associated with monogenic hereditary disorders with late-onset manifestation. Such diseases include: 1) neurodegenerative conditions caused by a specific type of so-called dynamic Mutations (Huntington's chorea, spinocerebellar ataxia, Machado–Joseph disease, Kennedy's disease, myotonic dystrophy), whose pathological effects appear only in adulthood; 2) Alzheimer's disease; 3) breast Cancer and familial adenomatous polyposis of the colon.

Pre-symptomatic Diagnosis of such disorders is of great importance, as preventive Treatment can delay the age of onset and allow for timely surgical intervention in cases of tumors. Diagnosis is based on the detection of mutations in disease-associated genes and is feasible in families burdened with a specific hereditary pathology.

Today, susceptibility genes have been identified for many Multifactorial Diseases (see Table 7.9).

For instance, polymorphism in the exon of the vitamin D3 receptor Gene (VDR3), certain alleles of the Collagen genes COL1A1 and COL2A1, and Calcitonin receptor genes indicate a predisposition to Osteoporosis. This condition is characterized by a reduction in bone mineral content, leading to a sharp increase in the likelihood of fractures. The disease is frequently diagnosed in women during the menopausal and postmenopausal periods.

Mutations in the low-density lipoprotein receptor (LDLR) gene lead to early-onset atherosclerosis and contribute to coronary artery disease and myocardial infarction. The predisposition to myocardial infarction is also associated with a polymorphism in the angiotensin-converting enzyme gene (a polymorphism linked to an Alu sequence deletion in intron 16, found in 30% of the population).

Susceptibility genes include the methylenetetrahydrofolate reductase (MTHFR) enzyme gene, whose point mutation at position 677 C-T occurs in a homozygous state in approximately 5% of the population. This polymorphism causes hyperhomocysteinemia, which in turn correlates positively with CORONARY Heart DISEASE, atherosclerosis, and The Development of congenital neural tube defects (anencephaly, Spina bifida, and encephalocele). Administering Folic acid to carriers of the mutant genes prevents the development of these pathological features.

Mutations of the CC16 gene have been identified that, in the homozygous state (10% of the population), correlate with asthma. Mutations in the coagulation factor V gene dramatically increase the risk of thrombosis. Allelic polymorphisms of the TGF2 gene correlate with cleft lip and cleft palate.

Susceptibility gene testing makes it possible to identify individuals with an increased risk of developing specific pathologies. The mere presence of unfavorable alleles does not necessarily mean the onset of the disease is inevitable. In multifactorial disorders, environmental factors play a crucial role in Etiology. Through preventive measures, the risk of developing the pathology can be significantly reduced.