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The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression.

Owing to unprecedented merits such as high theoretical capacity, superior energy density and low cost, lithium-sulfur batteries (LSBs) show a bright future both in scientific and industrial areas. Whereas, the inherent issues, including highly insulating character, undesired shuttle behavior and lithium dendrites growth, are seriously impeding its practical usage. Here, a metal-organic-frameworks (MOFs) derived N, S co-doped carbon nanotube hollow architecture confining with CoS2 nanoparticles (CoS2/NSCNHF) modified separator is designed to surmount these obstacles. Compared with Celgard separator, this designed separator shows obviously enhanced flame retardancy, giving 73.1% and 53.0% reductions in peak heat release rate and total heat release, separately. Concretely, its hollow structure, conductive feature, electrocatalytic activity and Lewis acid-base interaction enable the efficient inhibition on shuttle behavior as well as boost in polysulfides conversion kinetics. The cell with modified separator delivers a high discharge capacity of 1,284.5 mAh·g−1. After running for 100 cycles, a discharge capacity of 661.3 mAh·g−1 is remained. Markedly, the suppression on lithium dendrites growth is also observed, manifesting the enhanced battery safety. Overall, this work may shed light on the effective usage of MOFs-derived hierarchical composite in achieving LSBs with high electrochemical performance as well as safety.

Chromosome microarray analysis (CMA) has proven to be a powerful tool in postnatal patients with intellectual disabilities. However, the diagnostic capability of CMA in patients with congenital oral clefts remain mysterious. Here, we present our clinical experience in implementing whole-genome high-resolution SNP arrays to investigate 33 patients with syndromic and nonsyndromic oral clefts in whom standard karyotyping analyses showed normal karyotypes. We aim to identify the genomic aetiology and candidate genes in patients with congenital oral clefts. CMA revealed copy number variants (CNVs) in every patient, which ranged from 2 to 9 per sample. The size of detected CNVs varied from 100 to 3.2 Mb. In 33 patients, we identified six clinically significant CNVs. The incidence of clinically significant CNVs was 18.2% (6/33). Three of these six CNVs were detected in patients with nonsyndromic clefts, including one who presented with isolated cleft lip with cleft palate (CLP) and two with cleft palate only (CPO). The remaining three CNVs were detected in patients with syndromic clefts. However, no CNV was detected in patients with cleft lip only (CLO). The six clinically significant CNVs were as follows: 8p23.1 microduplication (198 kb); 10q22.2-q22.3 microdeletion (1766 kb); 18q12.3 microduplication (638 kb); 20p12.1 microdeletion (184 kb); 6q26 microdeletion (389 kb); and 22q11.21-q11.23 microdeletion (3163 kb). In addition, two novel candidate genes for oral clefts, KAT6B and MACROD2, were putatively identified. We also found a CNV of unknown clinical significance with a detection rate of 3.0% (1/33). Our results further support the notion that CNVs significantly contributed to the genetic aetiology of oral clefts and emphasize the efficacy of whole-genome high-resolution SNP arrays to detect novel candidate genes in patients with syndromic and nonsyndromic clefts.

Hemoglobin H disease is the most severe non-fatal form of α-thalassemia syndrome characterized by pronounced microcytic hypochromic hemolytic anemia. It is predominantly seen in Southeast Asia, the Middle East and the Mediterranean. Studies suggest that hemoglobin H disease is not as benign a disorder as previously thought. Newborn screening for hemoglobin H disease is especially appealing because the screening test is based on the detection of hemoglobin Bart’s (γ4) that is only possible within the newborn period. In this study, we reported on a 4-year period of newborn screening program at a mainland Chinese hospital, which detected 35 babies with hemoglobin H disease in a total of 26 152 newborns. The overall prevalence for hemoglobin H disease among all newborns in southern China is ~1 in 1,000. These children need appropriate follow-up and potential comprehensive care during their growth and development.

To study the prevalence of non-detectable chromosomal abnormalities by quantitative fluorescent polymerase chain reaction (QF-PCR) in a Chinese population referred for amniocentesis.The karyotype results were reviewed in 8,466 amniotic fluid cultures performed for positive fetal Down syndrome screening or advanced maternal age between January 2002 and June 2012. The karyotype results were classified as detectable or not detectable by QF-PCR, using the assumption that all tests were conducted by this rapid molecular method.Of the 8,466 karyotypes obtained, 211 abnormal karyotypes were found (2.5%). Out of these, 168 cases of common aneuploidies were identified by QF-PCR, and 43 cases of chromosomal abnormalities were missed. The 43 cases missed by QF-PCR included 31 cases predicted to confer no increased risk and 12 with a potential clinical significance. When QF-PCR shows a normal result, the overall residual risk is 0.1% for any clinically significant chromosomal abnormality.A normal QF-PCR result predicts a very low residual risk for patients who are referred solely for an increased risk of a common trisomy.

In this paper beta-globin gene mutations were detected in 452 beta-thalassemia carriers from 13462 unselected individuals (6731 pregnant women and their husbands) who were screened for the beta-thalassemia trait in the Guangzhou area of China. The incidence of beta-thalassemia was calculated as 3.36%. This is higher than found in previous studies performed in southern China. Using reverse dot blot analysis, we found 11 types of mutations and identified the mutations in 446 (98.7%) of the 452 cases. Direct sequencing was carried out on the 6 unknown alleles, and a novel amber mutation in a beta 0-thalassemia gene (beta 37TGG --TAG) was found in one of them. Thus, the prevalence and spectrum of beta-thalassemia mutations were obtained for this region. Twelve couples were detected at risk for thalassemia, and prenatal diagnosis was carried out in 11 of them. This is the largest number of Chinese subjects studied by DNA analysis to date and is the first report on the prospective diagnostic trial for beta-thalassemia in a Chinese population. In addition, we have performed 80 prenatal diagnoses based on screening for beta-thalassemia retrospectively.

Dear Editor, β-Thalassemia is a heterogeneous genetic disease associated with defective expression of the β-chain of human hemoglobin. So far, more than 200 mutations have been defined and affect almost every known stage of β-globin gene expression resulting in a reduction (β) or complete absence (β) of β-chain synthesis from the affected allele [1, 2]. In southern China, the carrier rate of β-thalassemia in Guangdong province was 2.54% [3], with five common mutations accounting for 90% of all β-thalassemia individuals. Identification of new mutations and update of the mutation spectrum of thalassemia in one specific ethnic population is always needed for improving genetic counseling and prenatal diagnosis. We here describe a novel promoter mutation of −50 (G→A) within the conserved direct repeat element (DRE) leading to β-thalassemia major when associated with a β-thalassemia mutation. A 3-year-old Chinese boy with his parents was seen at our genetics clinic. The boy suffered from β-thalassemia major and had been transfused every 2 months since the age of 6 months. Molecular analyses performed by reverse dot blots (RDB) at other clinics revealed that he was a heterozygote for the common mutation of codons (CDs) 41–42 (−TTCT) of the β-globin gene, but the other mutational allele was not determined. At this referral, the family was planning for another pregnancy and counseled about prenatal diagnosis. Blood samples were obtained from all three family members. Hematological investigations showed that both of the parents had a classical β-thalassemia trait and the son manifested with severe β-thalassemia (Table 1). Determination of the β-thalassemia mutations was performed using the polymerase chain reaction (PCR)–RDB method which can simultaneously detect 17 types of β-globin gene mutations found in Chinese population. This confirmed the heterozygous presence of the CDs 41–42 (−TTCT) mutation in the son and the father, but the mutation was not found in the mother. Gap PCR was also undertaken in the three family members to exclude the coinheritance of αthalassemia, and this did not reveal any of the three common Chinese α-globin gene deletion mutations (−α, −α, –). To further investigate the underlying mutation in this family, the β-globin gene was amplified by PCR from DNA of the mother, and the product was analyzed by direct nucleotide sequencing using the BigDyeTM Terminator Cycle Sequencing Kit and the ABI PRISMTM 310 genetic analyzer (Applied BioSystems). Direct sequencing of the β-globin gene showed the normal sequence except for the heterozygous G→A mutation at position −50 relative to the Cap site (Fig. 1). This so far undescribed mutation was also revealed in the son by DNA sequencing. Thus the patient was confirmed to be a compound heterozygote with a genotype of −50 (G→A)/CDs 41–42 (−TTCT). In order to evaluate the functional effect of this novel mutation, two other family members were investigated. A semiquantitative reverse transcription PCR assay was used to measure β globin mRNA in the reticulocytes from three heterozygous subjects (the mother, grandmother, and an aunt) and eight normal individuals. These analyses showed a mildly reduced β-globin mRNA level (23.4 %) in heterozygotes compared with that in normal subjects. Ann Hematol (2009) 88:1149–1150 DOI 10.1007/s00277-009-0732-8