Routine antenatal molecular testing for α-thalassemia at a tertiary referral hospital in China: ten years of experience

TL;DR

This study shows that routine α-thalassemia gene testing during pregnancy in China over ten years helped prevent severe cases and reduced costs.

Contribution

The study proposes new cutoff points for α-thalassemia screening that could reduce costs while maintaining diagnostic accuracy.

Findings

α-thalassemia mutations were found in 41.78% of 91,852 patients tested over ten years.

New cutoff points for screening could save approximately 10 million yuan by reducing missed diagnoses.

Prenatal diagnosis identified four cases of fetal anemia and two of severe fetal edema.

Abstract

This study aimed to evaluate the efficacy of α-thalassemia gene testing as a part of an antenatal intervention program over a 10-year period.

All patients underwent α-thalassemia gene testing, which included the analysis of three types of deletions and mutations. Rare α-thalassemia gene testing was performed using Sanger sequencing, multiplex ligation-dependent probe amplification, and sequencing techniques. Prenatal diagnosis was performed in high-risk couples using chorionic villus sampling or amniocentesis.

From 2010 to 2019, among the 91,852 patients examined, α-thalassemia mutations were identified in 41.78% of patients. The most frequent α0 gene mutation was--SEA, followed by--THAI. Two rare α0-thalassemia gene mutations at --32.8 and --230, were also observed. A total of 2,235 high-risk couples were identified, of which 562 were affected, including three with the--SEA/--THAI genotype and one with the--SEA/--230 genotype. Additionally, prenatal diagnosis revealed four cases of fetal anemia and/or mild edema, along with two cases of severe fetal edema. Chromosome and gene chip results were normal. Thalassemia gene testing showed an αCSα/αCSα genotype in four patients with anemia and/or mild edema, while two patients with severe fetal edema had one--SEA/αCSα genotype and one--SEA/--GX genotype. Using the cut-off points of 74.6 fL and 24.4 pg as criteria for identifying α0-thalassemia carriers and HbH disease, the detection rate of missed diagnoses in high-risk couples is consistent with national guidelines for standards, potentially saving 10,217,700 ¥.

Routine molecular testing for α-thalassemia in high-risk prenatal populations effectively prevented severe α-thalassemia births. Despite the high cost, the cutoff points proposed by this study suggest that implementing screening using a new parameter has the potential to reduce current expenses.

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