# Detection of Rare Thalassemia Variants Using Accurate Circular Consensus Long‐Read Sequencing

## TL;DR

This study shows that accurate circular consensus long-read sequencing can detect rare thalassemia gene variants that traditional methods miss.

## Contribution

The study demonstrates the effectiveness of a novel sequencing method in identifying rare thalassemia variants.

## Key findings

- Accurate circular consensus long-read sequencing identified 16 additional rare thalassemia cases.
- The method detected 12 point variants and 4 deletion variants in the thalassemia gene.
- This sequencing approach improves detection rates for rare thalassemia carriers.

## Abstract

The aim of this study is to evaluate the efficacy of accurate circular consensus long‐read sequencing in the detection of rare thalassemia.

Conventional molecular analysis on globin genes has limitations because of the broad spectrum of genetic variants, complex genetics, and genotype–phenotype correlation. Accurate circular consensus long‐read sequencing is a novel tool that detects complex variants in the thalassemia gene based on third‐generation sequencing. In this study, we screen out suspected rare thalassemia carriers by hemoglobin analysis and conventional molecular analysis, and evaluate the efficacy of accurate circular consensus long‐read sequencing in the detection of rare thalassemia.

Based on the traditional screening of thalassemia gene, an additional 16 (17.67%) cases of clinically significant variants of rare thalassemia were identified by accurate circular consensus long‐read sequencing in this study, including 12‐point variants and 4 deletion variants: HBB: (SEA)‐HPFH, HBB: c.268_281delAGTGAGCTGCACTG, HBB: (Chinese) Gγ + (Aγδβ)0, and HBA2:c.91‐93delGAG.

Accurate circular consensus long‐read sequencing has a promising prospect in detecting rare thalassemia gene variants and may improve the detection rate of carriers.