Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated ...

Frequencies of spontaneous and proflavine-induced frameshift mutations increase dramatically as a function of the number of reiterated base pairs at each of two sites in the lysozyme gene of bacteriophage T4. At each site, proflavine induces addition mutations more frequently than deletion mutations. We confirm that the steroidal diamine, irehdiamine A, induces frameshift addition mutations. At...

Mutation rates are generally thought not to be influenced by selective forces. This doctrine rests on the results of certain classical studies of the mutations that make bacteria resistant to phages and antibiotics. We have studied a strain of Escherichia coli which constitutively expresses a lacI-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion to Lac+ is a rare eve...

Lipoid congenital adrenal hyperplasia (LCAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. We report novel molecular findings of three unrelated infants with LCAH diagnosed at our center. A known missense mutation c.653C>T (p.A218V) and two novel mutations [premature termination c.441G>A (or p.W147X) and frameshift deletion c.del815G (or p.R272PfsX35)] were identifie...

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother wh...

PURPOSE The authors report the ophthalmic characteristics of a male proband in a Japanese family with autosomal dominant optic atrophy (DOA) harboring a frameshift mutation in the OPA1 gene. METHODS Conventional ophthalmologic examinations including static automated perimetry were performed, as well as assessment of the three-generation family history. The peripapillary retinal nerve fiber la...

Germline mutations in the BRCA1 tumour suppressor gene on chromosome 17q21 are responsible for approximately half of the cases of hereditary breast cancer, including the majority of familial breast/ovarian cancers. To increase our knowledge of the spectrum of BRCA1 mutations, we have extended our analysis to include patients with varied family histories of cancer of the breast, ovary, and at mu...

We report a case of a 56-year-old woman with breast cancer, ovarian cancer, and diffuse large B-cell lymphoma with a BRCA1 gene mutation. Evidence is mounting that there is a large increase in the risk for hematologic malignancies among patients with genetic changes in the BRCA pathways. The genomic analysis demonstrated a frameshift mutation in the BRCA1 gene: 277_279delinsCC (Phe93fs). It is ...

Neurofibromatosis type 1, also known as NF1 or von Recklinghausen's disease, is a common neurocutaneous syndrome that presents with multiple café-au-lait patches, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. The mutations of the gene NF1, encoding the protein neurofibromin, have been identified as the cause of this disease. Here, we report a clinical and molecular stud...

Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally that frameshift mutation rates in yeast microsatellites depend on the genomic context and that this variation primarily reflects the context-dep...