Invasive molecular prenatal diagnosis of alpha and beta thalassemia among Hakka pregnant women.

Heming Wu,Mei Zeng,Huichao Zhu,Zhiyuan Zheng,Jie Wu,Wei Guo,Liubing Lan,Huaxian Wang,Pingsen Zhao

doi:10.1097/md.0000000000013557

Abstract

This study is a retrospective analysis of the prenatal genetic diagnosis results of fetuses with high risk of major thalassemia to provide information for clinical genetic counseling and to better control the birth of major thalassemia child in Hakka population. Totally, 467 fetuses in at-risk pregnancies were collected from Meizhou people's hospital from January 2014 to December 2017. Genomic DNAs were extracted from peripheral blood of the couples and villus, amniotic fluid or cord blood of the fetuses. DNA-based diagnosis was performed using polymerase chain reaction (PCR) and flow-through hybridization technique. Follow-up visits were done half a year after the fetuses were born. Around 467 fetus at-risk pregnancies were performed prenatal diagnosis. We detected 88 CVS samples, 375 amniocentesis fluid samples and, 4 cord blood samples. The 356 fetuses in α-thalassemia families consisted of 69 (19.38%) with Bart's hydrops syndrome, 20 (5.62%) fetuses with Hb H disease, and 184 (51.68%) fetuses with heterozygote. And the 111 fetuses in β-thalassemia families consisted of 31 (27.93%) thalassemia major, 51 (45.95%) fetuses with heterozygote. There are 13 fetuses with α+β-thalassemia, including 2 cases with severe β-thalassemia. DNA-based testing prenatal diagnosis of thalassemia was found to be highly reliable. Our findings provide key information for clinical genetic counseling of prenatal diagnosis for major thalassemia in Hakka pregnant women. Our work plays an important role in the prevention and control of thalassemia in Hakka population. We will also combine other techniques to further improve our molecular prenatal diagnostic capabilities, including the next-generation sequencing (NGS), Sanger sequencing and MLPA.

Highlights

Thalassemia is considered to be one of the most common genetic diseases in the world, with a high frequency in tropical and subtropical regions such as Mediterranean countries, Indian subcontinent, Middle East, North Africa, and South Ocean.[1,2] There are high incidences in Guangxi, Guangdong, and Hainan province of China.[3,4,5,6] Thalassemia is an autosomal recessive disease characterized by microcytic hypochromic anemia resulting from the congenital defect of human globin gene, resulting in inadequate or complete loss of the corresponding globin chain synthesis and the imbalance of the ratio between alpha chain and nonalpha chain in hemoglobin, giving rise to moderate or severe hemolytic anemia
The parents with b-thalassaemia showed that Hb A2 was beyond 3.5% and mean corpuscular volume (MCV) was
DNA-based diagnosis was performed on the tissues of fetuses who have risk with severe thalassemia using polymerase chain reaction (PCR) and flow-through hybridization technique

Summary

Introduction

Thalassemia is considered to be one of the most common genetic diseases in the world, with a high frequency in tropical and subtropical regions such as Mediterranean countries, Indian subcontinent, Middle East, North Africa, and South Ocean.[1,2] There are high incidences in Guangxi, Guangdong, and Hainan province of China.[3,4,5,6] Thalassemia is an autosomal recessive disease characterized by microcytic hypochromic anemia resulting from the congenital defect of human globin gene, resulting in inadequate or complete loss of the corresponding globin chain synthesis and the imbalance of the ratio between alpha chain and nonalpha chain in hemoglobin, giving rise to moderate or severe hemolytic anemia.

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