Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment.

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity. Although investigation with human induced pluripotent stem cell models has confirmed disruption of neuronal development in 16p11.2del neuronal cells, which genes are responsible for abnormal cellular phenotypes and what determines the penetrance of neurodevelopmental abnormalities are unknown. We performed haplotype phasing of the 16p11.2 region in a 16p11.2del neurodevelopmental disorders cohort and generated human induced pluripotent stem cells for two 16p11.2del families with distinct residual haplotypes and variable neurodevelopmental disorder phenotypes. Using transcriptomic profiles and cellular phenotypes of the human induced pluripotent stem cell-differentiated cortex neuronal cells, we revealed MAPK3 to be a contributor to dysfunction in multiple pathways related to early neuronal development, with altered soma and electrophysiological properties in mature neuronal cells. Notably, MAPK3 expression in 16p11.2del neuronal cells varied on the basis of a 132 kb 58 single nucleotide polymorphism (SNP) residual haplotype, with the version composed entirely of minor alleles associated with reduced MAPK3 expression. Ten SNPs on the residual haplotype were mapped to enhancers of MAPK3. We functionally validated six of these SNPs by luciferase assay, implicating them in the residual haplotype-specific differences in MAPK3 expression via cis-regulation. Finally, the analysis of three different cohorts of 16p11.2del subjects showed that this minor residual haplotype is associated with neurodevelopmental disorder phenotypes in 16p11.2del carriers.

Disruption of the ADAM17/NF-κB feedback loop in astrocytes ameliorates HIV-1 Tat-induced inflammatory response and neuronal death.

A disintegrin and metalloproteinases (ADAMs) are involved in multiple neurodegenerative diseases. However, the roles and mechanisms of ADAMs in HIV-associated neurocognitive disorder (HAND) remain unclear. Transactivator of transcription (Tat) induces inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. In this study, we determined that ADAM17 expression was upregulated during soluble Tat stimulus in HEB astroglial cells. Inhibition of ADAM17 suppressed Tat-induced pro-inflammatory cytokines production and rescued the astrocytes-derived conditioned media (ACM)-mediated SH-SY5Y neural cells apoptosis. Moreover, ADAM17 mediated Tat-triggered inflammatory response in a NF-κB-dependent manner. Conversely, Tat induced ADAM17 expression via NF-κB signaling pathway. In addition, pharmacological inhibition of NF-κB signaling inhibited Tat-induced inflammatory response, which could be rescued by overexpression of ADAM17. Taken together, our study clarifies the potential role of the ADAM17/NF-κB feedback loop in Tat-induced inflammatory response in astrocytes and the ACM-mediated neuronal death, which could be a novel therapeutic target for relief of HAND.

Putative regulators for the continuum of erythroid differentiation revealed by single-cell transcriptome of human BM and UCB cells.

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34-CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP, and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation.

Kinesiophobia and related factors in cancer patients with TIAPs during the long term: a cross-sectional survey.

OBJECTIVE: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs). METHODS: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia. RESULTS: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia. CONCLUSION: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects.

Pediatric esophagogastroduodenoscopy in china: indications, diagnostic yield, and factors associated with findings.

BACKGROUND: Large-scale data on esophagogastroduodenoscopy (EGD) in China are scarce. This study aimed to assess the indications and diagnostic yield of EGD in children and the relationship between factors (such as age, sex, and indications) and diagnostic yield. METHODS: We performed a prospective cross-sectional observational study involving patients aged < 18 years who underwent diagnostic EGD. The study was conducted in five children's hospitals, each in a different city. Demographic features, indications for endoscopy, and endoscopic and histopathological findings were collected. Univariable and multivariable ordinal logistic regression analyses of the relationship between the factors and diagnostic yield were performed. RESULTS: The study included 2268 patients (male/female ratio, 1.3:1) with a median age of 8.68 years. Among the 2268 children, the most frequent indications were abdominal pain in 1954 (86.2%), recurrent vomiting in 706 (31.1%), weight loss in 343 (15.1%), and others. The endoscopic yield was 62.5% and was the highest in patients with dysphagia (90.9%). The histologic yield was 30.4% and was the highest in patients with unexplained anemia (45.5%). On multivariable regression analysis, the endoscopic yield was associated with dysphagia, gastrointestinal (GI) bleeding, and recurrent vomiting, and the histologic yield was associated with age. Different groups of patients with abdominal pain had variable probabilities of abnormal endoscopic findings. CONCLUSIONS: The most frequent indication of pediatric EGD is abdominal pain, with variable probabilities of abnormal endoscopic findings in different groups. Endoscopic yield and histologic yield are associated with certain alarming features. TRIAL REGISTRATION: The trial registration number (ClinicalTrials. gov): NCT03603093 (The study was registered on 27/07/2018).

HIF-1α downregulation of miR-433-3p in adipocyte-derived exosomes contributes to NPC progression via targeting SCD1.

Resident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte-derived exosomes are key information carriers that transfer low expression of miR-433-3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor-1α (HIF-1α) induced miR-433-3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR-433-3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl-CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor-bearing mice, NPC cells with low HIF-1α expression, high miR-433-3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF-1α-miR-433-3p-SCD1 axis in NPC progression, which can serve as a mechanism-based potential therapeutic approach.

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg-1 ·d-1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 µM), which was attenuated by co-treatemnt with puerarin (100 µM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 µM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Profiling and bioinformatics analyses reveal differential expression of circular RNA in tongue cancer revealed by high-throughput sequencing.

Circular RNAs (circRNA) are special noncoding RNAs. They are widely present, but with unknown functions. Recent studies have shown that many endogenous circRNAs have sponge function to absorb microRNAs (miRNA). They can regulate target gene messenger RNA expression and play important roles in many biological processes. However, expression profile and function of circRNAs in human tongue squamous cell carcinoma (TSCC) have not been reported. High-throughput sequencing was performed to identify and annotate from three TSCC tissues and adjacent tissues. A separate set (n = 20) of human TSCCs and corresponding adjacent tissues were subjected to reverse-transcription polymerase chain reaction (RT-PCR) for validation of circRNAs expression profile. Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA-miRNA network analysis were also performed to predict the function of circRNA in TSCC. A total of 12 156 circRNAs were identified and annotated, most of the circRNAs were novel ( n = 6231) and exonic (62.09%). Statistical analysis revealed 322 differentially expressed (DE) circRNAs. RT-PCR results showed that circRNA expression in TSCC was higher than that in adjacent tissues. GO functional analysis, KEGG pathway analysis, and circRNA-miRNA network analysis all showed that circRNAs correlated with tumor development and progression to a certain extent. The current study is the first to systematically characterize and annotate circRNA expression in TSCC, the majority were novel circRNAs. Some host genes of the DE circRNAs were involved in tumor signaling pathway and had complicated correlations with tumor-relevant miRNAs, indicating that circRNAs might be promoted development and progression of TSCC.

Nitazoxanide, an anti-parasitic drug, efficiently ameliorates learning and memory impairments in AD model mice.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of ß-amyloid (Aß) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aß clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aß clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3ß pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg-1·d-1, ig) for 100 days. Furthermore, NTZ administration decreased Aß level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

[Genetic testing and pregnancy outcome of 337 fetuses with urinary system anomalies].

OBJECTIVE: To explore the genetic basis and pregnancy outcome of fetuses with urinary system anomalies. METHODS: Ultrasonographic features, genetic testing and pregnancy outcomes of 337 fetuses with urinary system anomalies identified by prenatal ultrasonograhy were collected for analysis. RESULTS: Ultrasonographic features of the fetuses were mainly characterized by hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia. Thirty four fetuses (10.1%) were found to harbor a genetic defect, including 14 numerical chromosomal disorders, 10 structural chromosomal aberrations, and 10 pathogenic copy number variations (CNVs). In 31 cases, the parents elected induced labor. For the 303 fetuses with negative findings, 142 were born by spontaneous delivery or Caesarean section, 48 cases underwent induced labor, 1 case had miscarriage, and the remaining 112 cases had unknown or missed pregnancy outcomes. CONCLUSION: Hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia are the most common findings among fetuses with urinary system anomalies. Approximately 10.1% of such fetuses are positive by genetic testing.

Discovery of novel purine nucleoside derivatives as phosphodiesterase 2 (PDE2) inhibitors: Structure-based virtual screening, optimization and biological evaluation.

Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders and pulmonary hypertension. Herein, we identified that clofarabine (4), an FDA-approved drug, displayed potential PDE2 inhibitory activity (IC50 = 3.12 ±â€¯0.67 µM) by structure-based virtual screening and bioassay. Considering the potential therapeutic benefit of PDE2, a series of purine nucleoside derivatives based on the structure and binding mode of 4 were designed, synthesized and evaluated, which led to the discovery of the best compound 14e with a significant improvement of inhibitory potency (IC50 = 0.32 ±â€¯0.04 µM). Further molecular docking and molecular dynamic (MD) simulations studies revealed that 5'-benzyl group of 14e could interact with the unique hydrophobic pocket of PDE2 by forming extra van der Waals interactions with hydrophobic residues such as Leu770, Thr768, Thr805 and Leu809, which might contribute to its enhancement of PDE2 inhibition. These potential compounds reported in this article and the valuable structure-activity relationships (SARs) might bring significant instruction for further development of potent PDE2 inhibitors.

Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment.

Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodone-tacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 ±â€¯0.08 nM; 2a, EC50 = 0.58 ±â€¯0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 ±â€¯6.60 nM; 2a, IC50 = 22.10 ±â€¯5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 ±â€¯0.217 µM, BuChE IC50 = 0.34 ±â€¯0.03 µM; 2a, AChE IC50 = 2.36 ±â€¯0.34 µM, BuChE IC50 = 0.10 ±â€¯0.01 µM). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment.

The prevalence and molecular characterization of (뫧)0 -thalassemia and hereditary persistence of fetal hemoglobin in the Chinese Zhuang population.

OBJECTIVE: To reveal the prevalence and molecular characterization of (δß)0 -thalassemia [(δß)0 -thal] and hereditary persistence of fetal hemoglobin (HPFH) in the Chinese Zhuang population. METHODS: A total of 105 subjects with fetal hemoglobin (Hb F) level ≥5% from 14 204 unrelated ones were selected for the study. Multiplex ligation dependent probe amplification was firstly used to analyze dosage changes of the ß-globin gene cluster for associated with (δß)0 -thal and HPFH mutations. The gap polymerase chain reaction was then performed to identify the deletions using the respective flanking primers. Hematologic data were recorded and correlated with the molecular findings. RESULTS: Twenty-one (0.15%) subjects were diagnosed with Chinese G γ(A γδß)0 -thal. Nine (0.06%) were diagnosed with Southeast Asia HPFH (SEA-HPFH) deletion. Seventy-five (0.53%) cases remained uncharacterized. Three genotypes for Chinese G γ(A γδß)0 -thal and SEA-HPFH deletion were identified, respectively. The genotype-phenotype relationships were discussed. CONCLUSION: Our study for the first time demonstrated that (δß)0 and HPFH were not rare events, and molecular characterized G γ(A γδß)0 -thal and HFPH mutations in the Chinese Zhuang population. The findings in our study will be useful in genetic counseling and prenatal diagnostic service of ß-thalassemia in this populations.

Identification of a Novel 9.7 kb Deletion Causing α0-Thalassemia in Two Pregnant Women in Southern China.

The technique of combining multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (CGH) and gap-polymerase chain reaction (gap-PCR) is an effective way to locate unknown breakpoints on the α-globin genes. In the current report, a novel deletion was detected in two pregnant women with moderate hematological phenotypes. Multiplex ligation-dependent probe amplification and array CGH revealed a probable 9.7 kb deletion at 16p13.3. The breakpoints were precisely defined by gap-PCR and direct sequencing. This deletion (NG_000006.1: g.32709_42418del) included HBA1, HBA2 and HBQ, which resulted in an α0-thalassemia (α0-thal) mutation. There would be a 25.0% chance of conceiving an α-thal intermedia or α-thal major (α-TI or α-TM) fetus if the couples are both carriers. Rare large deletions can cause α-thalassemia (α-thal) and the structure analysis of an unknown deletion is important for clinical diagnosis and further genetic counseling.

First Identification of the 3.5 kb Deletion (NC_000011.10: g.5224302-5227791del3490bp) on the ß-Globin Gene Cluster in a Chinese Family.

ß-Thalassemia (ß-thal) is one of the most common autosomal recessive disorders worldwide. It is caused mainly by point mutations or, more rarely, deletions on the ß-globin gene, leading to reduced (ß+) or absent (ß0) synthesis of the ß chains of hemoglobin (Hb). Molecular characterization of ß-thal is essential for the prevention of this disease in the population. In China, more than 46 different mutations have been found, while approximately five large deletional types of ß-thal have been reported. Here we described a large deletional mutation of the ß-globin gene cluster previously unreported in the Chinese population, the 3.5 kb deletion (NC_000011.10: g.5224302-5227791del3490bp) removing the ß-globin gene promoter and the whole ß-globin gene leading to a ß0-thal phenotype.

Characterization of Hb Bart's Hydrops Fetalis Caused by - -SEA and a Large Novel α0-Thalassemia Deletion.

Hb Bart's hydrops fetalis is the most severe and generally fatal clinical phenotype of α-thalassemia (α-thal), which is due to the deletion of all four functional α-globin genes of hemoglobin (Hb), resulting in no α-globin chain production (- -/- -). Homozygosity for the - -SEA (Southeast Asian) α-globin gene deletion is the main cause of the Hb Bart's hydrops fetalis in Asia, especially South China. Occasionally, other α0-thal deletions can also be found. In this study, we report a case with an atypical form of Hb Bart's hydrops fetalis that was caused by - -SEA and a large novel α0-thal deletion (- -GX) (Guangxi). The fetus with Hb Bart's in our study presented fetal hydrops features in early gestation which was different from that of traditional Hb Bart's hydrops fetalis with a homozygous - -SEA deletion. The early onset of fetal hydrops is attributed to the decreased formation of embryonic Hb Portland (ζ2γ2), which is proposed as a candidate for reactivation in cases of severe α-thal. Our findings indicated that it was important to characterize new or rare mutations, and highlighted the significance of using ultrasonography to identify signs of Hb Bart's hydrops fetalis.

Achaete-scute complex homologue-1 promotes development of laryngocarcinoma via facilitating the epithelial-mesenchymal transformation.

Laryngeal cancer is one of the most common fatal cancers among head and neck carcinomas, whose mechanism, however, remains unclear. The proneural basic-helix-loop-helix protein achaete-scute complex homologue-1, a member of the basic helix-loop-helix family, plays a very important role in many cancers. This study aims to explore the clinical value and mechanism of achaete-scute complex homologue-1 in laryngeal cancer. Methods including Cell Counting Kit-8, flow cytometry, Transwell invasion assays, and scratch assay were adopted to further explore the bio-function of achaete-scute complex homologue-1, whose expression was examined in fresh and paraffin chip of laryngeal carcinoma tissues by means of western blot and immunohistochemistry, after the interference of achaete-scute complex homologue-1; achaete-scute complex homologue-1, an overexpression in laryngeal carcinoma whose carcinogenicity potential was confirmed via western blot, was correlative with T classification (p = 0.002), histological differentiation (p = 0.000), lymph node metastasis (p = 0.000), and poor survival (p = 0.000). Multivariate analysis shows that achaete-scute complex homologue-1 overexpression is an independent prognostic factor unfavorable to laryngeal carcinoma patients (p = 0.000). Moreover, knocking down achaete-scute complex homologue-1 expression could significantly suppress the proliferation, migration, and invasion of laryngeal carcinoma cell in vitro and disorder epithelial-mesenchymal transformation-associated protein expression. Achaete-scute complex homologue-1 plays an important role in the genesis and progression of laryngeal carcinoma and may act as a potential biomarker for therapeutic target and prognostic prediction.

A Novel Mutation of the α2-Globin Gene Causing α+-Thalassemia: Hb Nanning (HBA2: c.369_370delinsGA).

We report a novel mutation on the α2-globin gene, Hb Nanning (HBA2:c.369_370delinsGA) detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by various separation techniques. Both carriers of the mutation have mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values that are below normal, as would be predicted for an α+-thalassemia (α+-thal) patient.

A Novel α2-Globin Gene Mutation: Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T].

We report a novel mutation on the α2-globin gene, Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. Hb Debao was associated with an α+-thalassemia (α+-thal) deletion [-α3.7 (rightward)] producing a mild phenotype with significant microcytosis and hypochromia, while the combination of this mutation with an α0-thal deletion (--SEA) resulting in a severe form of Hb H (ß4) disease, which is consistent with a thalassemic phenotype associated with the novel mutation.

Complex Interaction of Hb Q-Thailand with α0- and ß0-Thalassemia in a Chinese Family.

Hb Q-Thailand [α74(EF3)Asp→His (α1); HBA1: c.223 G>C] is an abnormal hemoglobin (Hb), variant found mainly in China and Southeast Asian countries. The association of the αQ-Thailand allele with other globin gene disorders has important implications in diagnosis. Here, we report a hitherto undescribed condition of patients with a double heterozygosity for Hb Q-Thailand with α0-thalassemia (α0-thal) and in combination with ß0-thalassemia (ß0-thal) in a Chinese family. Our study will provide some clinical manifestations, laboratory diagnosis and genetic counseling for complex hemoglobinopathies.