Thalassemia screening by third-generation sequencing: Pilot study in a Thai population

Area of Science:

• Genetics
• Molecular Biology
• Medical Diagnostics

Background:

• Conventional thalassemia screening methods are stepwise and have limitations in identifying the full spectrum of genetic mutations.
• Accurate and comprehensive genetic diagnosis is crucial for effective thalassemia management.

Purpose of the Study:

• To evaluate the performance of third-generation sequencing (TGS) in comparison to conventional molecular testing for thalassemia.
• To determine TGS's ability to validate known variants and detect previously unidentified mutations.

Main Methods:

• Third-generation sequencing (TGS) was employed to analyze samples from patients with suspected or known thalassemia.
• The study involved validating variants identified by conventional testing and searching for novel variants in undiagnosed cases.
• Data was collected from Maharaj Nakorn Chiang Mai Hospital between December 2021 and April 2022.

Main Results:

• Out of 19 cases, 52.6% had known thalassemia variants, while 47.7% remained undiagnosed by conventional methods.
• TGS successfully validated all 16 previously detected variants.
• TGS identified additional thalassemia variants in 36.8% of cases, uncovering 43.8% of the total variants detected.

Conclusions:

• Third-generation sequencing (TGS) provides superior diagnostic yield for thalassemia compared to conventional molecular testing.
• TGS can identify additional genetic variants, improving the diagnosis of thalassemia in complex cases.
• Further research, including cost-effectiveness studies with larger cohorts, is recommended to establish TGS in routine clinical practice.