Clinical characteristics and gene mutation analysis of an adult patient with ETFDH­related multiple acyl­CoA dehydrogenase deficiency.

Multiple acyl­CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder of fatty acid metabolism caused by defects in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These defects are mainly classified into the neonatal and late­onset types, based on their clinical manifestations. ETFDH gene mutations are generally considered to be associated with the late­onset type. The present study reported an adult woman with late­onset MADD accompanied with biochemical and muscle biopsy findings indicating metabolic disorders. Gene sequencing analysis showed that the c.1514T>C homozygous mutation in the region of the 12th exon of the ETFDH gene, which led to the amino acid substitution p.I505T (isoleucine > threonine), resulting in defective ETFDH protein function. The results of family verification revealed that the homozygous mutation originated from her parents. The female patient was treated with a large dose of vitamin B2, L­carnitine and coenzyme Q10, and the symptoms were significantly relieved. The c.1514T>C mutation in the ETFDH gene, was considered as a novel pathogenic mutation that had not been previously reported. Therefore, it was hypothesized that this mutation was responsible for the clinical characteristics of the adult female patient. Overall, this novel mutation could expand the spectrum of the ETFDH gene mutation and provide the basis for the etiological and prenatal diagnosis of MADD.

Analysis of angiographic characteristics and intervention of vitamin D in type 2 diabetes mellitus complicated with lower extremity arterial disease.

AIMS: Previous studies have suggested that type 2 diabetes mellitus with lower extremity arterial disease is related to 25-hydroxyvitamin D deficiency. The purpose of this study is to explore the relation between vitamin D supplementation and the characteristics of type 2 diabetes mellitus complicated with lower extremity arterial disease. METHODS: The clinical data of 514 patients and 148 healthy subjects treated in the First Hospital of Lanzhou University from January 2012 to June 2019 were collected, including the clinical data, ankle-brachial index, and medical records of lower limb artery angiography. We divided the patients into control group (NC group), type 2 diabetes mellitus group (DM group), lower extremity artery disease in type 2 diabetes mellitus without vitamin D supplement group (DM1 group) and lower extremity artery disease in type 2 diabetes mellitus with vitamin D supplement group (DM2 group). The level of serum 25(OH)D was analyzed and the characteristics of arterial lesions of lower extremities were compared by DSA arteriography in DM1 and DM2 group, respectively. RESULTS: Compared with the NC group, serum 25(OH)D level decreased in DM group (25.39 ± 4.94 ng/mL vs 19.43 ± 5.98 ng/mL) and significantly decreased in DM1 and DM2 group (14.22 ± 5.64 ng/mL vs 17.36 ± 6.25 ng/mL). However, the level of serum 25(OH)D in the DM2 group was higher than that in the DM1 group. Compared with the DM1 group, the disease rate of the inferior knee artery (65% vs 39.3%) and occlusion rate (11.5% vs 3.7%)were decreased in the DM2 group (P < 0.05). Logistic stepwise regression analysis showed that serum 25(OH)D level was a risk factor for lower extremity arterial disease in patients with type 2 diabetes mellitus (OR = 0.898,95%CI = 0.856-0.942). CONCLUSIONS: The serum level of 25(OH)D in patients with type 2 diabetes mellitus complicated with lower extremity arterial disease is decreased, and level of 25 (OH) D is related to stenosis and occlusion rate, especially in inferior genicular artery in T2DM complicated with LEAD. A high level of 25(OH)D may be a protective factor in type 2 diabetes with lower extremity arterial disease.

Exposure of single-stranded telomeric DNA causes G2/M cell cycle arrest in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, Cdc13p is a single-stranded TG(1-3) DNA binding protein that protects telomeres and maintains telomere length. A mutant allele of CDC13, cdc13-1, causes accumulation of single-stranded TG(1-3) DNA near telomeres along with a G(2)/M cell cycle arrest at non-permissive temperatures. We report here that when the single-stranded TG(1-3) DNA is masked by its binding proteins, such as S. cerevisiae Gbp2p or Schizosaccharomyces pombe Tcg1, the growth arrest phenotype of cdc13-1 is rescued. Mutations on Gbp2p that disrupt its binding to the single-stranded TG(1-3) DNA render the protein unable to complement the defects of cdc13-1. These results indicate that the presence of a single-stranded TG(1-3) tail in cdc13-1 cells serves as the signal for the cell cycle checkpoint. Moreover, the binding activity of Gbp2p to single-stranded TG(1-3) DNA appears to be associated with its ability to restore the telomere-lengthening phenotype in cdc13-1 cells. These results indicate that Gbp2p is involved in modulating telomere length.