Single-gene disorders, which result from structural abnormalities or malformations in a single gene within an individual’s DNA chain, belong to a group of diseases that affect organs or tissues due to genetic mutations. Approximately 4,000 single-gene disorders have been identified to date, underscoring the significance of early diagnosis and intervention.

PGT for Single-Gene Disorders

Preimplantation Genetic Testing for Monogenic Diseases (PGT-M) is a remarkable advancement in addressing single-gene disorders. This procedure allows for the selection of healthy embryos that do not carry the genetic mutations responsible for these diseases in couples at risk of passing them on to their children.

Prenatal Diagnosis During Pregnancy

Early diagnosis of single-gene disorders often occurs during pregnancy or shortly after birth. Genetic tests for both parents can determine whether the baby will inherit the disease. Prenatal diagnostic tests can identify whether the fetus carries the genetic mutation or is merely a carrier. Two commonly used methods for this diagnostic testing are:

  1. Amniocentesis: This procedure involves collecting a small amount of amniotic fluid surrounding the fetus and is typically performed between 15 and 20 weeks of pregnancy.
  2. Chorionic Villus Sampling (CVS): CVS entails taking a small biopsy from the placenta using a special needle, often done between 10 and 13 weeks of pregnancy.

Early Diagnosis Through Newborn Screening

In recent years, many countries have implemented newborn screening programs for early diagnosis of cystic fibrosis and other monogenic diseases. In these programs, a relatively inexpensive test analyzes immunoreactive trypsinogen (IRT) levels in a blood sample obtained from the baby’s heel. Elevated IRT levels may indicate the need for further tests to confirm the diagnosis.

If initial tests show a high IRT level, genetic testing is performed for a definitive cystic fibrosis diagnosis. A positive result indicates that the baby has cystic fibrosis or is a carrier. To confirm the diagnosis, a sweat test is conducted shortly after.

Diagnosis for Children and Adults

For couples at risk of passing on single-gene disorders who were not screened during pregnancy or at birth, various tests are available for diagnosis.

Sweat Test

The sweat test is considered the gold standard for diagnosing cystic fibrosis and is typically performed on individuals exhibiting typical cystic fibrosis symptoms. However, in cases with atypical clinical findings, chloride levels in sweat may not be sufficient for a definitive diagnosis. Rarely, individuals with positive genetic tests may have negative sweat test results. Furthermore, certain other conditions can also lead to positive sweat test results.

Mutation Analysis – Genetic Testing

Mutation analysis is a test used to diagnose single-gene disorders by detecting specific genetic mutations associated with the disease. Scientists have identified over 2,000 mutations that can potentially lead to these disorders by producing faulty forms of specific proteins. These mutations vary in frequency and distribution among different populations. Achieving a mutation detection rate of over 95% in the mutation analysis panel for these disorders can be challenging in some populations due to the rarity of certain mutations.