Background: There are limited reports available on investigations into the molecular spectrum of thalassemia and hemoglobinopathy in Fujian province, Southeast China. Here, we aim to reveal the spectrum of the thalassemia mutation and hemoglobinopathy in Quanzhou prefecture, Fujian province.Methods: We collected data from a total of 17,407 subjects with the thalassemia trait in Quanzhou prefecture. Gap-PCR, DNA reverse dot blot hybridization, and DNA sequencing were utilized for common and rare thalassemia gene testing.Results: In our study, we identified 7,085 subjects who were carrying thalassemia mutations, representing a detection rate of 40.70% (7,085/17,407). Among them, 13 different α-thalassemia gene mutations were detected, with the most common mutation being –SEA (69.01%), followed by –α3.7 (21.34%) and –α4.2 (3.96%). We also discovered 26 β-thalassemia gene mutations, with the mutations of IVS-II-654 (C > T) (36.28%) and CD41/42(–TCTT) (29.16%) being the most prevalent. Besides, a variety of rare thalassemia variants were identified. Among them, the –FIL, βMalay, βIVS–I–130, and βIVS–II–672 mutations were identified in Fujian province for the first time. Additionally, we detected 78 cases of hemoglobinopathies, of which Hb Owari was the first reported case in Fujian province and Hb Miyashiro was the first case identified in the Chinese population.Conclusion: Our study indicates that there is a diverse range of thalassemia mutations, and it also reveals the mutation spectrum of rare thalassemia and hemoglobinopathies in Quanzhou, Fujian province. It provides valuable data for the prevention and control of thalassemia in Southeast China.

AimsThalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and β-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China.MethodsA total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and β-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers.ResultsAmong 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --SEA/αα (71.47%), -α3.7/αα (17.13%) and -α4.2/αα (3.49%). 1407 (12.06%) subjects were β-thalassemia carriers, 18 types of β-thalassemia mutations were identified. The common five genotypes of β-thalassemia were βIVS-II-654/βN (36.53%), βCD41-42/βN (30.28%), βCD17/βN (17.13%), βCD26/βN (5.12%) and β-28/βN (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and β-thalassemia were identified. Furthermore, 9 α-thalassemia and β-thalassemia gene mutations (CAP +40–43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), −90 (C>T), CD3 (T>C), -α6.9) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and −90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α6.9 mutations were first identified in Chinese individual.ConclusionsQuanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.

BackgroundCopy number variations (CNVs) can contribute to human phenotype, phenotypic diversity and disease susceptibility, while others may benign. In the current study, an attempt to investigate the pathogenicity of CNVs in chromosome Xp22.31 was explored.MethodsG-banding and SNP-array techniques were used to analyze chromosome karyotypes and CNVs in fetuses. Parents associate with five different pedigrees possessing high risk factors in pregnancy were considered with such parameters as advanced age, high risk of serological screening and ultrasound abnormalities.ResultsThe fetuses’ amniotic fluid karyotypes were 46, XX and those of their parents with the five pedigrees revealed no abnormalities. Here, we noticed a series of individuals with Xp22.31 duplications ranging from 534.6 kb to 1.6 Mb. It was detected through SNP array that the fetuses in Pedigree 1 and 2 had ~ 600 kb duplications in the Xp22.31 region of their X chromosomes which contained two OMIM genes, HDHD1 (OMIM: 306480) and part of STS (OMIM: 300747). The fetuses of Pedigrees 3, 4 and 5 had 1.6 Mb duplication in the same chromosome which contained four OMIM genes: HDHD1 (OMIM: 306480), STS (OMIM: 300747), PNPLA4 (OMIM: 300102) and VCX (OMIM: 300229). The duplications in the fetuses of Pedigrees 1 and 5 were inherited from the non-phenotypic parents. Pedigrees 3 and 4 refused to perform parental verification. Finally, four of the five pedigrees continue towards pregnancy with no abnormalities being observed during followed-ups.ConclusionOur study first showed duplications of Xp22.31 in Chinese population. Clinical and genetic investigation on five different pedigrees, we consider the duplication of these fragments as likely benign copy number variants (CNVs). We suggest that the duplications of Xp22.31 with recurrent duplication as a benign CNVs .

Background α-thalassaemia is an inherited blood disorder caused by mutations in the α-globin gene cluster. Recognizing the pathogenic α-globin gene mutations associated with α-Thalassemia is of significant importance to thalassaemia’s diagnosis and management. Methods A family with α-thalassaemia from Fujian, China was recruited for this study. The phenotype was confirmed through haematological analysis. Commercially available Gap-PCR genotypic methods were employed to identify the known deletions causing α-thalassemia. MLPA analysis was used to study the novel mutations; this was then confirmed through DNA sequencing and bioinformatics analysis. Results The proband of the family belonged to Southeast Asian type (-- SEA ) thalassaemia. None of the known mutations associated with α-thalassaemia were detected in this family’s genetics, whereas a novel 6.9 kb deletion (16p13.3 g.29,785-36,746) covering the α2 gene on the globin gene cluster was identified with MLPA and confirmed through Sanger Sequencing. This data led us to propose a novel pathogenic deletion associated with α-thalassemia: -α 6.9 /-- SEA . Conclusions A novel α-thalassaemia deletion was identified in members of a Chinese family and subsequently analyzed. This finding has helped broaden the spectrum of pathogenic mutations leading to the development of α-thalassaemia, paving the way for improved disease diagnosis and management.

Background An increasing number of techniques have been used for prenatal diagnosis of genetic abnormalities. Our initial objective was to explore the value of the BACs-on-Beads (BoBs) assay for the prenatal diagnosis of aneuploidies and microdeletion/microduplication syndromes in Quanzhou, Southeast China. Methods A total of 1409 pregnant women with high-risk factors for chromosomal abnormalities admitted to Quanzhou Women’s and Children’s Hospital were enrolled in this study. BoBs assays and karyotype analyses were conducted for all subjects. Subsequently, chromosome microarray analysis (CMA) or fluorescence in situ hybridization (FISH) was performed to validate the findings. Results In this study, karyotype analysis and BoBs assay failed in 4 cases, and 2 cases, respectively. A total of 1403 cases were successfully analyzed, with success rates of 99.72% (1405/1409) and 99.85% (1407/1409) for karyotype analysis and Bobs assay, respectively. BoBs assay rapidly detected chromosomal aneuploidies in line with the karyotyping data. Additionally, 23 cases of microdeletions/microduplications were detected by BoBs assay but missed by karyotyping, including 22q11.2 microdeletions/microduplications, 5p15.32p15.33 microdeletion, Xp22.31 microdeletions/microduplications, Xq27.3 microdeletion, and Yp11.2 and Yq11.22q11.222 microduplication. In comparison with karyotyping, fewer mosaicisms were identified by BoBs assay. A high detection rate of chromosomal abnormalities was observed in the high-risk group during noninvasive prenatal testing (NIPT) (41.72%) and the abnormal ultrasound group (13.43%). Conclusions BoBs assay can be used for the rapid and efficient prenatal diagnosis of common aneuploidies and microdeletion/microduplication syndromes. Moreover, the combined use of BoBs assay and karyotyping in prenatal diagnosis may allow for a more effective detection of chromosomal abnormalities.

Context.— Identification of rare thalassemia variants requires a combination of multiple diagnostic technologies. Objective.— To investigate a new approach of comprehensive analysis of thalassemia alleles based on third-generation sequencing (TGS) for identification of α- and β-globin gene variants. Design.— Enrolled in this study were 70 suspected carriers of rare thalassemia variants. Routine gap–polymerase chain reaction and DNA sequencing were used to detect rare thalassemia variants, and TGS technology was performed to identify α- and β-globin gene variants. Results.— Twenty-three cases that carried rare variants in α- and β-globin genes were identified by the routine detection methods. TGS technology yielded a 7.14% (5 of 70) increment of rare α- and β-globin gene variants as compared with the routine methods. Among them, the rare deletional genotype of –THAI was the most common variant. In addition, rare variants of CD15 (G>A) (HBA2:c.46G>A), CD117/118(+TCA) (HBA1:c.354_355insTCA), and β-thalassemia 3.5-kilobase gene deletion were first identified in Fujian Province, China; to the best of our knowledge, this is the second report in the Chinese population. Moreover, HBA1:c.-24C>G, IVS-II-55 (G>T) (HBA1:c.300+55G>T) and hemoglobin (Hb) Maranon (HBA2:c.94A>G) were first identified in the Chinese population. We also identified rare Hb variants of HbC, HbG-Honolulu, Hb Miyashiro, and HbG-Coushatta in this study. Conclusions.— TGS technology can effectively and accurately detect deletional and nondeletional thalassemia variants simultaneously in one experiment. Our study also demonstrated the application value of TGS-based comprehensive analysis of thalassemia alleles in the detection of rare thalassemia gene variants.

Background: Very few reports are available on human XX ovotesticular disorder of sex development involving SOX3 gene duplication. Here we aim to present a rare case of SOX3 gene duplication in a person from the Chinese population who exhibits XX ovotesticular disorder of sex development.Case Presentation: A 7-year-old Chinese individual from Fujian province in Southeast China was recruited. The patient presented 46, XX karyotype, absence of sex-determining region Y, and was diagnosed with XX ovotesticular disorder of sex development. Furthermore, SNP array analysis demonstrated that the patient had a 2.2-Mb duplication in the Xq27.1q27.2 region (arr[hg19]Xq27.1q27.2:139,499,778-141,777,782) involving the SOX3 gene. Additionally, no SOX3 duplication was observed in the parents or the sibling, who displayed none of the clinical features.Conclusion: We identified the first case of SOX3 duplication in a Chinese individual who exhibits ovotesticular disorder of sex development. Our study strengthens the link between the SOX3 duplication and XX ovotesticular disorder of sex development and indicates that SOX3 is the evolutionary antecedent of sex-determining region Y.

Aims There is little knowledge about partial trisomy 4q and the genotype–phenotype correlation. In this study, we presented the detail of two Chinese families with partial distal 4q duplication in an attempt to clarify the correlation between the genotype and the phenotype. Methods Two pedigrees with distal 4q duplication were enrolled in this study. Karyotype analysis and single-nucleotide polymorphism (SNP) array detection were performed for prenatal diagnosis. Fluorescence in situ hybridization analysis. (FISH) was conducted to verify the copy number variants. Results Two families with partial trisomy 4q were identified. The fetus in pedigree 1 exhibited multiple ultrasound anomalies including intrauterine growth restriction and an atrioventricular septal defect who had a duplication of 4q28.3-qter associate with 6p25.2-p25.3 deletion, which resulted from balanced translocation carried by his father t(4;6)(q28.3;p25.2). The fetus in pedigree 2 had a distal 4q28.3-qter duplication combined with monosomy of Xp21.3-p22.3, and the karyotype was described as 46,X,der(X)t(X;4)(p21.3;q28.3)mat, which originally inherited from the pregnant woman who exhibited a mild clinical phenotype limited to short stature. Conclusions In our study, we for the first time identified the partial trisomy 4q associate with 6p or Xp deletion. In addition, our finding further strengthens that mild clinical phenotype in 4q duplication case may be due to the spreading of X inactivation to the autosomal in derivation of chromosome X.