Background: Thalassemia is one of the most prevalent inherited single gene diseases. Prevention of βthalassemia through prenatal diagnosis is the one of the most effective and direct approach to control the spread of this life-threatening disease. This study aims to determine the prenatal diagnosis of αthalassemia and β-thalassemia in 3049 families among eighteen regions of Hainan Province using molecular diagnosis.Methods: This study enrolled a total of 3049 couples and their fetuses at The First A liated Hospital of Hainan Medical University from January 2004 to March 2020. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic uid, or fetal cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction.Results: Here, the most commonly detected mutation of α-thalassemia was a South-East Asian deletion (31.53%), followed by -α 4.2 /αα (11.15%), -α 3.7 /αα (11.02%). The most common mutation for βthalassemia was CD41/42, followed by -28, accounting for 30.27% and 2.56%, respectively. The regions with the highest prevalence were the coastal regions and the regions with the lowest prevalence were Wenchang, Lingao and Ding'an. We also examined thalassemia gene mutations in Han people and other minority groups and found that the most common gene mutations in different ethnic were not homogeneous. Prenatal diagnosis showed 556 normal, 118 α-thalassemia hydrops and 161 βthalassemia major fetuses. Conclusion:Our ndings provide important information for clinical genetic counseling of prenatal diagnosis for thalassemia major in Hainan Province. Methods SubjectsThis study included pregnant women and their husbands who registered for a program of diagnosis of thalassemia at The First A liated Hospital of Hainan Medical University in Hainan Province between January 2004 and March 2020. All couples had resided in Hainan Province, and came from eighteen regions including Haikou,

Background: Thalassemia is one of the most prevalent inherited single gene diseases. Prevention of β-thalassemia through prenatal diagnosis is the one of the most effective and direct approach to control the spread of this life-threatening disease. This study aims to determine the prenatal diagnosis of α-thalassemia and β-thalassemia in 3049 families among eighteen regions of Hainan Province using molecular diagnosis.Methods: This study enrolled a total of 3049 couples and their fetuses at The First Affiliated Hospital of Hainan Medical University from January 2004 to March 2020. Genomic DNA was extracted from peripheral blood of the couples and villus, amniotic fluid, or fetal cord blood of fetuses. DNA-based diagnosis was performed using polymerase chain reaction. Results: Here, the most commonly detected mutation of α-thalassemia was a South-East Asian deletion (31.53%), followed by –α4.2/αα (11.15%), –α3.7/αα (11.02%). The most common mutation for β-thalassemia was CD41/42, followed by -28, accounting for 30.27% and 2.56%, respectively. The regions with the highest prevalence were the coastal regions and the regions with the lowest prevalence were Wenchang, Lingao and Ding’an. We also examined thalassemia gene mutations in Han people and other minority groups and found that the most common gene mutations in different ethnic were not homogeneous. Prenatal diagnosis showed 556 normal, 118 α-thalassemia hydrops and 161 β-thalassemia major fetuses. Conclusion: Our findings provide important information for clinical genetic counseling of prenatal diagnosis for thalassemia major in Hainan Province.

Fraser syndrome is a rare autosomal recessive malformation disorder. It is characterized by cryptophthalmos, syndactyly, urinary tract abnormalities and ambiguous genitalia. This condition is due to homozygous or heterozygous mutations in the FRAS1 , FREM1 , FREM2 , and GRIP1 genes . In the present study, we recruited a Chinese family with Fraser syndrome. Two novel mutations c.7542_7543insG and c.2689C>T in the FREM2 gene were detected in this Fraser syndrome family by PCR-based sequencing. The next-generation sequencing-based single nucleotide polymorphism haplotyping method was applied to exclude these two mutations in 9 blastocysts obtained from the patient. After obtaining consent and informing the risk, the patient received in vitro fertilization and embryo transfer treatment with an embryo carrying a heterozygous mutation. Finally, she delivered a healthy baby without any complications on March 17, 2019. In conclusion, we first reported two novel mutations in the FREM2 gene associated with the risk of Fraser syndrome. Moreover, we described a next-generation sequencing-based single nucleotide polymorphism haplotyping method to select the ‘right’ embryos from patients with Fraser syndrome for in vitro fertilization and embryo transfer treatment.