Nuances in ATP7B Genetic Testing and Interpretation in India

Area of Science:

• Genetics
• Metabolic Disorders
• Medical Diagnostics

Background:

• Wilson disease is a genetic disorder affecting copper metabolism, with aggressive hepatic variants in Indian children.
• Current diagnostic methods in India have limitations, leading to treatment delays.
• India's high endogamy and consanguinity rates contribute to a significant disease burden.

Purpose of the Study:

• To comprehensively review the utility and limitations of genetic testing for Wilson disease in India.
• To highlight challenges in diagnosis, variant interpretation, and genotype-phenotype correlation.
• To emphasize the need for population screening and improved diagnostic strategies.

Main Methods:

• Review of existing literature on Wilson disease genetics and diagnostics in India.
• Analysis of ATP7B gene variants reported in the Indian population.
• Discussion of current diagnostic practices versus genetic testing recommendations.

Main Results:

• Next-generation sequencing and exome sequencing are powerful tools for Wilson disease diagnosis, offering near-confirmatory results.
• Approximately 234 ATP7B variants are reported in India, with regional variations and three pan-Indian variants.
• Genotype-phenotype correlations remain largely inconclusive, particularly in the Indian context.

Conclusions:

• Genetic testing is crucial for early diagnosis and management of Wilson disease, especially for relatives and asymptomatic individuals.
• Current clinical-biochemical approaches in India are insufficient, necessitating wider adoption of genetic testing.
• Population screening and further research into genotype-phenotype correlations are essential for improving Wilson disease care in India.