Background and aims: Hemoglobinopathy associated with the HBB gene, with its two general subtypes as thalassemia and abnormal hemoglobin (Hb) variants, is one of the most prevalent hereditary Hb disorders worldwide. Herein we aimed to elucidate the prevalence of ß-thalassemia and abnormal hemoglobin variants and the prenatal diagnosis of the HBB gene in Jiangxi Province, southern central China.Methods: Hematological indices and capillary Hb electrophoresis were conducted for 136,149 subjects who were admitted to Jiangxi Maternal and Child Health Hospital and requested for hemoglobinopathy investigation. Routine α- and ß-globin genotyping were performed by gap-polymerase chain reaction (Gap-PCR) and reverse dot-blot (RDB) hybridization for the 11,549 individuals suspected to be thalassemia carriers. For participants whose genotypes could not explain their hematological indices, further Sanger sequencing and Gap-PCR were conducted for the detection of rare or novel variants in related globin genes. Prenatal diagnosis was performed for 77 pregnant couples both carrying ß-thalassemia trait at appropriate gestational ages.Results: Among the 11,549 subjects, 2,548 individuals were identified with HBB-associated hemoglobinopathy based on molecular analysis. A total of 2,358 subjects were identified as ß-thalassemia heterozygous carriers and nine cases were diagnosed as compound heterozygous ß-thalassemia. Additionally, 125 cases were detected with composite α- and ß-thalassemia and the remaining 56 individuals with abnormal Hb variants in the HBB. A total of 35 types of variants were identified in the HBB gene, including 26 types of ß-thalassemia and nine types of abnormal Hb variants. Four novel variants were firstly reported, including one variant in HBA2 and three variants in HBB. Overall, 77 prenatal samples underwent ß-thalassemia molecular diagnosis; 20 fetuses were identified with normal ß-thalassemia genotypes, 30 fetuses as ß-thalassemia heterozygotes, 11 as homozygotes, and 16 as compound heterozygotes in HBB.Conclusion: We have demonstrated a relatively high prevalence rate at 1.872% of ß-hemoglobinopathies including common and rare ß-thalassemia as well as abnormal Hb variants among large child-bearing population in the Jiangxi area of southern central China for the first time. Our data presents that prenatal diagnosis is an effective way to prevent and control birth defects of ß-thalassemia.

Purpose The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing for them. Methods Clinical examination, pedigree analysis, exome sequencing, minigene-based splicing analysis and in vivo RNA analysis were carried out on the family. Preimplantation genetic testing (PGT) for the causative variation and chromosome aneuploidis based on SNP analysis has been used to avoid transmission of hearing loss in this family. Results All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383 + 6T > A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the deafness phenotype in the extended family. Functional analysis of RNA indicated that c.5383 + 6T > A is a pathogenic splice-site variant and should be considered for diagnostic purposes. Furthermore, a successful singleton pregnancy with no variant in the site c.5383 + 6 within TECTA locus was established and a healthy male child was born by PGT. Conclusion We have identified a novel variant c.5383 + 6T > A in TECTA ZA-ZP inter-domain, which could be contributing to in early onset autosomal dominant hearing loss phenotype,The implications of our study are valuable in the clinical diagnosis, prognosis, and treatment of patients with TECTA pathogenic variants.

Prenatal exposure to nicotine that are mainly produced from tobacco smoke has been reported to affect infants. Therefore, nicotine exposure is one of important health concerns for newborn screening. Detecting nicotine and its metabolites such as cotinine in meconium were widely used to evaluate the tobacco exposure of pregnancy. In this study, disposable wooden tips were applied for touch sampling of meconium from newborn infants, and then were directly mounted on mass spectrometer (MS) to perform rapid screening of nicotine and cotinine. Choice of extraction/spray solvents was optimized. The limits of detection, reproducibility, linear response for direct analysis of meconium were also investigated. It is found the limits of detection (S/N = 3) to be as low as 0.36 ng/mg and 1.18 ng/mg for nicotine and cotinine, respectively, while the limits of quantitation (S/N = 10) to be 1.19 ng/mg and 3.94 ng/mg for nicotine and cotinine, respectively. The relative standard deviations (RSD) were found to be at 8.4%–19.8% (n = 6) for nicotine and cotinine, a good linear range from 5–500 ng/mL (R2 > 0.99). These analytical performances are well-accepted levels for ambient mass spectrometer analysis. In this study, evaluation of nicotine and cotinine in 22 puerpera volunteers were conducted by the established wooden-tip spray mass spectrometry (WTS-MS). These results showed that wooden-tip spray mass spectrometry would be useful for newborn screening of nicotine and cotinine in meconium with high reproducibility, speed, sensitivity, and specificity. Owing to the use of disposable wooden tips that involves no sample preparation and no chromatographic separation, our results show that wooden-tip spray mass spectrometry is a powerful tool for determination of nicotine in newborn meconium.