Laboratory Diagnosis by Genotyping

Area of Science:

• Genetics
• Molecular Biology
• Clinical Diagnostics

Background:

• Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that can lead to lung and liver diseases.
• Accurate diagnosis and variant identification are essential for patient management and genetic counseling.

Purpose of the Study:

• To highlight the utility of Alpha-1 antitrypsin (AAT) genotyping in clinical practice.
• To describe the reference standard methods for AAT variant identification.

Main Methods:

• Allele-specific genotyping assays for common variants (S, Z, Mmalton).
• Exome sequencing for comprehensive variant detection and characterization.
• Comparison of genotype with AAT levels and phenotypes.

Main Results:

• Genotyping confirms clinical diagnoses of AAT deficiency.
• It accurately identifies specific allelic variants, including rare and novel ones.
• Genotyping resolves discrepancies between measured AAT levels and predicted phenotypes.

Conclusions:

• AAT genotyping is the gold standard for diagnosing AAT deficiency and characterizing its genetic basis.
• It plays a vital role in confirming diagnoses, identifying rare variants, and resolving clinical ambiguities.