BACKGROUND Malignant hyperthermia susceptibility (MHS) is a life-threatening, inherited disorder of muscle calcium metabolism, triggered by anesthetics and depolarizing muscle relaxants. An unselected cohort was screened for MHS mutations using exome sequencing. The aim of this study was to pilot a strategy for the RYR1 and CACNA1S genes. METHODS Exome sequencing was performed on 870 voluntee...

The distal portion of chromosome 1p is one of the most commonly affected regions in human cancer. In this study of hereditary and sporadic colorectal cancer, a region of frequent deletion was identified at 32.2 centimorgans from 1ptel. Deletion breakpoints clustered in the vicinity of or inside the gene RIZ, which encodes a retinoblastoma protein-interacting zinc finger protein. Sequence analys...

The mutagenic properties of acridines on pneumococcus are described. All seven acridines tested were mutagenic at the amiA locus conferring a resistance to 10(-5) M aminopterin. The effects of quinacrine were more specifically investigated. It was observed that: mutants can be obtained only by treatment of exponentially growing cells; a sharp maximum mutagenic effect occurs at a concentration s...

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a 465-kDa catalytic subunit of DNA-PK, a DNA repair apparatus. DNA-PKcs has been reported to be a tumor suppressor, but details of its expression in human cancer are controversial. To determine the protein expression and clinical implications of DNA-PKcs in gastric carcinogenesis and cancer progression, we evaluated its expression sta...

Caveolae are small membrane invaginations found in vertebrates. Cavin-1 protein is essential for the homeostasis of caveolae. The frameshift mutation (p.Glu176Argfs) cavin-1 leads to physically debilitating condition known as congenital generalized lipodystrophy (CGL). Here we examined leucine zipper domain 2 (LZD2) and its CGL variant potential gain function through interaction with model memb...

Spontaneous loss of MupA-mediated high-level mupirocin resistance was observed in Staphylococcus aureus, although the isolate gave a PCR-positive test result for mupA. Sequencing of the mupA gene identified a single base-pair deletion that resulted in a frameshift mutation and loss of functional protein. Reversion to the wild-type allele and restoration of high-level resistance occurred with hi...

We describe the mutability of the Trp(-) chromosomal +1 frameshift mutation trpE7999 during nonlethal selection, finding that the appearance of Trp(+) revertants behaves similarly to that of episomal Lac(+) revertants. In addition, we show that a feature of the Lac(+) and Trp(+) mutability is the accumulation of Trp(+) and Lac(+) revertants with additional unselected mutations, most of which ar...

This study assessed the occurrence of hormetic dose responses from three previously published data sets [1-3] with 825 chemicals in three Ames assay tester strains (i.e., TA97, TA98, TA100) with and without the S9 fraction, using a five dose protocol and semi-log dose spacing. Ninety-five (95) (11.5%) chemicals satisfied the multiple a priori entry criteria, with a total of 107 assays. Of the a...

To date, approximately 200 different mutations in the MECP2 gene have been identified. We analyzed the entire coding sequence of the MECP2 gene and the X-chromosome inactivation pattern in 42 sporadic cases of Rett syndrome. Of the 42 patients, 30 had pathogenic mutations, including 14 different mutations: 9 missense mutations, 4 nonsense mutations, and 1 frameshift mutation. One was a novel mu...