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Objective: The thalassemias is a group of hereditary disorders with impaired production of functional hemoglobin. In this report we described a rare case of compound heterozygous mutation of South-East Asia type hereditary persistence of fetal hemoglobin (SEA-HPFH) and β -thalassemia that allowed prenatal diagnosis to be performed in a subsequent pregnancy in the family. Case report: The father showed a SEA-HPFH thalassemia trait phenotype, while his genotype revealed that he was heterozygous for the SEA-HPFH deletion; The mother genotype was heterozygote for IVS-II-654 mutation; the second child had co-inherited both parental mutations and was, thus, a compound heterozygote for β-thalassemia (IVS-II-654)/SEA-HPFH deletion. His phenotype was intermediate β-thalassemia. Prenatal genotyping of a fetal sample during the third pregnancy confirmed the fetus was only heterozygote for SEA-HPFH deletion and the parents elected to continue the pregnancy. Conclusion: We described the clinical and molecular characterization of the first detected case of compound β-Thalassemia/SEA-HPFH deletion in Northern Vietnam. The report also highlighted the accuracy and necessity of mutation screening for families with thalassemia to inform accurate genetic counseling and targeted prenatal diagnosis when desired.

Context: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown. Objective: To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM. Methods: Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells. Results: Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic fux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury. Conclusion: Our fndings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM. [ABSTRACT FROM AUTHOR]

Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletionalHbHdisease. The(- -SEA) type of α°-thalassemiamutation was detected in the majority of patients (>95%).Themost common genotype was (- -SEA/-α3.7), followed by (- -SEA/αcsα). After further investigation of the genotype-phenotype correlation in 68 patients, we found that patients with nondeletional Hb H disease had more severe clinical features than those with deletional Hb H disease, including younger age at diagnosis, more requirement of blood transfusions, and larger proportion of patients with splenomegaly, hepatomegaly or jaundice. This is probably a consequence of the lower hemoglobin levels and the higherHbHlevels. The clinical severity was highly variable even among patients with an identical genotype, and the diversity wasmuchmore profound among patients with (- -/αcsα) genotype. Therefore, predicting the phenotype directly from the genotype in Hb H disease remains relatively difficult in Taiwan. [ABSTRACT FROM AUTHOR]