The -α3.7III subtype of α+-thalassemia was identified in China
Xiuqin Bao1,2,3, Jicheng Wang1,2,3, Danqing Qin1,2,3
1Medical Genetics Center, Guangdong Women and Children Hospital, Guangzhou, People's Republic of China.
Insights
The -α3.7 III subtype of alpha-thalassemia was identified in China for the first time. This finding means all known -α3.7 subtypes are now found in the Chinese population, impacting prenatal diagnosis.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Alpha-thalassemia, characterized by the 3.7 kb deletion (-α3.7), is prevalent in Southern China with a 4.78% carrier rate.
- Globally, three subtypes of -α3.7 deletions have been identified.
- The -α3.7 III subtype had not been previously reported in China.
Purpose of the Study:
- To report the first identification of the -α3.7 III deletion subtype in a Chinese patient.
- To document the presence of all known -α3.7 deletion subtypes within the Chinese population.
Main Methods:
- Utilized gap-PCR and a liquid chip system for initial detection of alpha-thalassemia mutations.
- Employed multiple ligation-dependent probe amplification (MLPA) for detecting large deletions.
- Confirmed genotypes through Sanger sequencing and single molecule real-time (SMRT) sequencing.
Main Results:
- Identified the proband as a carrier of the -α3.7 III heterozygous deletion.
- Observed microcytosis and hypochromic red blood cells in the proband (MCV 78 fL, MCH 25.4 pg).
- Determined the mutation was inherited from the father, who presented with normal blood parameters.
Conclusions:
- This study marks the first identification of the -α3.7 III subtype in China.
- All previously identified -α3.7 deletion subtypes are now accounted for in the Chinese population.
- Clinical prenatal diagnosis requires increased attention to the -α3.7 III subtype, as common methods like gap-PCR may risk misdiagnosis or missed detection.
Objective:
The 3.7 kb deletion (-α3.7) in the α-globin cluster, which characterizes α+-thalassemia, has been reported to have a carrier rate of 4.78% in southern China. Three -α3.7 subtypes have been identified worldwide. However, the -α3.7 III subtype has not previously been identified in China. Herein, we reported identification of the -α3.7 III subtype in a Chinese patient.
Methods:
We used gap-PCR and a liquid chip system to detect α-thalassemia mutations. Multiple ligation-dependent probe amplification was performed to detect the large deletion. We finally used Sanger sequencing and single molecule real-time sequencing to characterize and confirm the genotype.
Results:
The proband, characterized as -α3.7 III heterozygous, showed microcytosis and hypochromic red cells, with a mean corpuscular volume of 78 fL and mean corpuscular hemoglobin of 25.4 pg. The proband's mutation was inherited from her father, who had normal blood parameters.
Conclusion:
We first identified the -α3.7 III subtype in China. Consequently, all -α3.7 subtypes have now been identified in the Chinese population. Therefore, attention should be paid to -α3.7 III in clinical prenatal diagnosis, given that commonly used methods such as gap-PCR may lead to misdiagnosis or missed diagnosis.
