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Monogenic diseases: causes, diagnosis and real cases
What are monogenic diseases?
Monogenic diseases are a group of inherited conditions that result from mutations in a single gene. They are relatively rare, but they have severe clinical manifestations and often require early diagnosis. According to the Mayo Clinic, an average of one in 100 children is born with a monogenic disorder.
The mutation can be dominant (one copy of the altered gene is enough) or recessive (two copies are needed, one from each parent). There are also cases where the pathology is transmitted through the X chromosome or mitochondria.
Typical examples of monogenic diseases
| Disease | Gene | Type of inheritance | Frequency |
|---|---|---|---|
| Cystic fibrosis | CFTR | Autosomal recessive | 1:2,500 (Europe) |
| Phenylketonuria | PAH | Autosomal recessive | 1:10,000 (Ukraine) |
| Marfan syndrome | FBN1 | Autosomal dominant | 1:5,000 |
| Huntington's disease | HTT | Autosomal dominant | 1:20,000 |
| Achondroplasia | FGFR3 | Autosomal dominant | 1:25,000 |
| Lesch-Nyhan syndrome | HPRT1 | Linked to the X chromosome | Very rare |
Real clinical examples
Case 1: Cystic fibrosis in an infant
In Kyiv, at the Center for Orphan Diseases, a 7-month-old boy was diagnosed with cystic fibrosis after repeated pneumonia and insufficient weight gain. Genetic analysis revealed two mutations in the CFTR gene. The therapy started with inhalations and enzymes allowed the child's condition to stabilize.
Case 2: Huntington's disease in a 40-year-old man
A resident of Lviv complained of impaired coordination and personality changes. A complicated family history (mother died of similar symptoms at age 50) prompted doctors to conduct a test for the HTT gene. The result confirmed the presence of CAG repeats above the norm - a classic marker of Huntington's disease.
Case 3: Prenatal diagnosis of phenylketonuria
A couple whose first child had phenylketonuria sought testing during their second pregnancy. An amniocentesis was performed at 16 weeks, which revealed a defect in both copies of the PAH gene. Thanks to this advance knowledge, the parents and doctors were prepared to provide special nutrition for the child from the very first days.
Diagnostic methods
DNA sequencing
Modern sequencing allows to detect mutations with high accuracy. Technologies like NGS (Next Generation Sequencing) are used in genetic panels and allow testing dozens of genes at a time.
PCR and Sanger sequencing
The PCR method is suitable for point detection of known mutations, while Sanger sequencing is used to confirm NGS results or analyze a specific gene.
Prenatal diagnosis
Performed in high risk or known carrier parents. Available methods: amniocentesis, chorionic biopsy, non-invasive fetal DNA testing (NIPT).
Treatment
Many monogenic diseases currently have no radical treatment, however:
Cystic fibrosis — combination therapy is used: inhalations, mucolytics, enzymes, specific drugs (ivacaftor).
Phenylketonuria — a strict diet with phenylalanine restriction.
Gaucher disease — enzyme replacement therapy (imiglucerase).
Mitochondrial diseases — metabolic support and vitamin therapy.
Genetic counseling
If a mutation is detected in one of the parents, counseling allows you to calculate the risk in future children. Usually, the consultation is conducted by a geneticist together with a bioethicist and a pediatrician.
Monogenic diseases are becoming increasingly diagnosed thanks to advances in genetic technologies. Early detection can change a family's life by reducing complications, improving prognosis, and choosing the right treatment path.
