Clinical application of long-read sequencing in newborn genetic screening for congenital adrenal hyperplasia.

Long-read sequencing combined with biochemical screening improves detection of congenital adrenal hyperplasia, identifying pathogenic CYP21A2 mutations in 1 in 20,029 neonates.

• Why it matters: Current screening relying solely on 17α-hydroxyprogesterone has limited accuracy, risking missed or incorrect diagnoses of CAH in newborns, which can lead to severe health consequences.
• What they did: Researchers conducted retrospective and prospective studies involving over 100,000 neonates, applying long-read sequencing alongside traditional biochemical tests to detect genetic mutations associated with CAH.
• The result: The integrated approach successfully identified all confirmed CAH cases and revealed additional heterozygous carriers, demonstrating that combining genetic testing with biochemical screening enhances diagnostic accuracy and carrier detection.