Whole exome sequencing reveals two novel compound heterozygous mutations in TWNK as a cause of the hepatocerebral form of mitochondrial DNA depletion syndrome: a case report.

BACKGROUND: Although Mitochondrial DNA depletion syndrome (MDS) can be classified into three forms: myopathic, encephalomyopathic and hepatocerebral form, it is difficult to identify its form due to its clinical heterogeneity. Therefore, it is very important to conduct molecular genetic analysis on suspected patients. This study presented a male 38 weeks and 5 days infant with liver cytolysis and leukodystrophy. CASE PRESENTATION: A male infant proband was admitted to the department of NICU for feeding intolerance, irregular rhythm of respiration, hypoglycemia, lactic acidosis, liver cytolysis and neurological abnormalities. He was onset of mild jaundice with leukodystrophy and high lactate and phenylderivatives for urine organic acids on the 7th day. Whole exome sequencing (WES) and Sanger sequencing were performed to screen and confirm the suspicious pathogenic mutations. The results revealed this proband carried two compound heterozygous mutations in TWNK: c.1186 C > T / p.Pro396Ser and c.1844 G > C / p.Gly615Ala inherited by an autosomal recessive form from his parents, of which protein conservative analysis and structural modeling supported the pathogenicity of the two mutations. Unfortunately, the conditions described above were not improved until he was discharged from the hospital on the 23rd day and died at 4 months of age. CONCLUSIONS: In this study, we investigated a Chinese family with the hepatocerebral form of MDS and conducted WES and Sanger sequencing to explore the causative mutations for this proband born from non-consanguineous and healthy parents. We identified two novel TWNK c.1186 C > T/ c.1844 G > C compound heterozygous mutations which were probably the disease-causing mutations of hepatocerebral form of MDS and described the clinical manifestations of the proband, which expanded the phenotypic spectrum of MDS caused by variants in TWNK. This study also emphasized WES technology can provide the genetic diagnosis of Mendelian genetic disease.

Effects of Klotho polymorphisms on Preeclampsia risk in a case-control study.

Preeclampsia (PE) is a serious disorder of human pregnancy and always is accompanied with multi-organ disorder, which severely threatens the health of both the mothers and the offspring. The oxidative stress and genetic factors involves in the development of PE. The Klotho encodes Klotho protein that is capable of increasing resistance to oxidative stress. Thus, we designed this case-control study to investigate the association between Klotho polymorphisms and the susceptibility to PE in Chinese Han women. Two single nucleotide polymorphisms (SNPs) (rs1207568 and rs564481) in Klotho were selected to be genotyped in 1002 PE patients and 1384 normal controls with TaqMan allelic discrimination real-time PCR technology. There were no significant differences in genotypic or allelic frequencies at both polymorphic sites between PE patients and controls (rs1207568: χ2 = 2.386, p = 0.303 by genotype, χ2 = 2.357, p = 0.125, OR = 1.127, 95%CI 0.968-1.312 by allele; rs564481: χ2 = 1.195, p = 0.550 by genotype, χ2 = 0.018, p = 0.894, OR = 1.010, 95%CI 0.875-1.165 by allele). Furthermore, we divided the cases into mild vs severe and early-onset vs late-onset subgroups and then analyzed the relationships between these subgroups and the control group respectively. As a consequence, no significant differences were found for both SNPs in each case. These results suggested that the genetic variants of rs1207568 and rs564481 in Klotho may not play a pivotal role in the pathogenesis of PE in Chinese Han women.

Novel THRB mutation analysis in congenital hypothyroidism with thyroid dysgenesis.

Thyroid dysgenesis (TD) accounts for most cases of congenital hypothyroidism. Although mutations in thyroid hormone receptor ß (THRB) have been identified in TD, the mutational spectrum of THRB and phenotype-genotype correlations have not been fully elucidated. In this study, we aimed to find mutations of THRB, examine the functions of these mutations, and attempt to elucidate the relationship between THRB and TD. Thus, we screened the exons of THRB in 280 patients with TD and 200 normal subjects in samples collected from China. We performed cell morphology assays, MTT assays, flow cytometric analyses, and a quantitative reverse-transcription polymerase chain reaction in human thyroid follicular epithelial cells (Nthy-ori cell line) to examine the impact of THRB mutations. In two unrelated patients, two novel missense mutations, c.76G>A (p.D26N) and c.107G>A (p.C36Y), were identified in THRB. Functional studies suggested that the C36Y mutant caused changes in morphology, inhibiting cell proliferation and promoting apoptosis in a human thyroid cell line. In addition, we found that messenger RNA expressions of thyroglobulin (TG) and the Na+ /I- symporter (NIS) were decreased in a time-dependent manner in mutant THRB compared with the wild type. To our knowledge, this is the first study to document the prevalence of THRB mutations and the genotype-phenotype spectrum of TD in a Chinese population. We characterized the function of a C36Y mutation, which reduced cell proliferation and increased cell death in thyroid epithelial cells. This study provides further evidence for genetic THRB defects and disease mechanisms in TD.

Colorful Hydrophobic Poly(Vinyl Butyral)/Cationic Dye Fibrous Membranes via a Colored Solution Electrospinning Process.

Colorful nanofibrous membranes have attracted much attention for their visual varieties and various functionalities. In this article, a colored solution electrospinning process was used to fabricate colorful hydrophobic poly(vinyl butyral) (PVB)/cationic dye nanofibrous membranes (NFMs) successfully. The color and morphology of these as-spun nanofibrous membranes have been analyzed by colorimetry, spectroscopy, and scanning electron microscopy (SEM). It is shown that the as-spun colorful PVB-based membranes exhibit excellent level-dyeing property and color stability. Furthermore, the doping of cationic dye and the increase of dye concentration can decrease the diameter of the as-spun colored fibers, which results in better level-dyeing property and higher water contact angle more than 140°. The stained PVB fibrous membranes with excellent level-dyeing property and hydrophobicity are promising in some applications such as textiles, wallpapers, and anticorrosive coating/painting.

In situ precise electrospinning of medical glue fibers as nonsuture dural repair with high sealing capability and flexibility.

PURPOSE: In this work, we propose an in situ precise electrospinning of medical glue fibers onto dural wound for improving sealing capability, avoiding tissue adhesion, and saving time in dural repair. METHODS: N-octyl-2-cyanoacrylate, a commercial tissue adhesive (medical glue), can be electrospun into ultrathin fibrous film with precise and homogeneous deposition by a gas-assisted electrospinning device. RESULTS: The self-assembled N-octyl-2-cyanoacrylate film shows high compactness and flexibility owing to its fibrous structure. Simulation experiments on egg membranes and goat meninges demonstrated that this technology can repair small membrane defects quickly and efficiently. CONCLUSION: This method may have potential application in dural repair, for example, working as an effective supplementary technique for conventional dura suture.