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E M Stone

Publications and source records attributed to E M Stone.

At least 163 records · Page 9Linked to original sources
PubMed1991

Ocular findings associated with a rhodopsin gene codon 58 transversion mutation in autosomal dominant retinitis pigmentosa.

Eight members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-guanine (C-to-G) transversion mutation in the second nucleotide of codon 58 of the rhodopsin gene, causing a substitution of the amino acid arginine for threonine. Five of these individuals were examined clinically. There was a distinct phenotypic expression of the gene defect within this family that included a regional predilection for pigmentary changes in the inferior and inferonasal parts of the retina, as well as field impairment predominantly in the superior hemisphere. Characteristic electroretinographic recordings and psychophysical threshold profiles also helped to identify this phenotype that, on a relative basis, causes less severe photoreceptor cell functional impairment than often occurs in other subtypes of retinitis pigmentosa. This report documents the association of a clinically recognizable phenotype in a family with autosomal dominant retinitis pigmentosa and a specific gene defect at the molecular level.

Adult↗
PubMed1991

Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene.

Mutations in the rhodopsin gene are associated with as many as one quarter of all cases of autosomal dominant retinitis pigmentosa (RP). A number of different rhodopsin mutations have been reported but only the proline to histidine mutation in codon 23 (Pro-23-His) has been well characterized clinically. One recent report described a "sectoral" distribution of the retinal degeneration associated with this mutation, while another reported only that pigment was present in all four quadrants in 13 of 17 patients. This asymmetric distribution of pigmentation and visual field loss may prove to be an important clinical sign of a type of RP with a relatively good visual prognosis. The authors present a family with Pro-23-His rhodopsin-associated RP in which all six affected individuals had a regional distribution of the retinal degeneration in which the inferior hemisphere of the retina was most severely affected.

Adolescent↗
PubMed1991

The SIR1 gene of Saccharomyces cerevisiae and its role as an extragenic suppressor of several mating-defective mutants.

The SIR1 gene product of Saccharomyces cerevisiae is one of several proteins involved in repressing transcription of the silent mating-type genes. Strains with mutations in the genes coding for these proteins are defective in mating due to derepression of the silent loci. We have found that overexpression of the SIR1 gene suppresses the mating defects of several of these mutants, including nat1 and ard1 mutants (the products of these two genes are responsible for N-terminal acetylation of a subset of yeast proteins), certain sir3 mutants, and a histone H4 mutant. The SIR1 gene has been sequenced and found to contain an open reading frame coding for a 678-amino-acid protein.

Amino Acid Sequence↗
PubMed1991

Protein phosphatases in cell division: how vital are they?

In contrast to the wealth of information on cellular function of protein kinases, many of which are known to be the products of proto-oncogenes, little is known about how protein dephosphorylation is involved in growth control of normal and malignant cells. In the present study, roles of protein phosphatases in cell division cycle control were examined by molecular genetic approaches using a lower eukaryote, the fission yeast Schizosaccharomyces pombe. Nine protein phosphatase genes have been so far identified and characterized in this organism. Each of two (dis2+, sds21+, and ppa1+, ppa2+) gene products is highly similar to mammalian type 1 and 2A ser/thr phosphatases, respectively. The ppx1+ product is an intermediate of type 1 and 2A, while the ppb1+ product is similar to Ca(2+)-dependent type 2B. At least two protein tyrosine phosphatase genes (pyp1+ and pyp2+) exist. The cdc25 protein is now established to be a tyrosine phosphatase that activates cdc2 kinase. Some of these phosphatase genes are interrelated but have distinct, essential functions in cell cycle control. Missense mutations, deletions or high dosage expression of these phosphatase genes affect entry into and exit from mitosis, mitotic chromosome disjunction, cell size and cell shape. They seem to interact with the main regulators of mitosis, cdc2, cdc13/cyclin, cdc25 and weel, or with mitotic structural components, such as condensed chromosomes or the spindle apparatus. We show that the product of an essential gene, sds22+, is an important, positive factor in controlling the expression and modulating the activity of dis2 phosphatase.

Amino Acid Sequence↗
PubMed1991

Difficulty differentiating Leber's from dominant optic neuropathy in a patient with remote visual loss.

A 31-year-old man who inexplicably lost vision as a child was referred for evaluation of bilateral optic atrophy. Other family members had also suffered unexplained visual loss. He had asymmetric impairment of visual acuity, central scotomas, and optic disc pallor. He also had a tritan color vision defect and excavation of the temporal portion of his optic discs, two features that were consistent with autosomal dominant optic atrophy. However, examination of the mitochondrial DNA of the proband and of two of his relatives revealed a mutation at nucleotide 11778, known to be associated with Leber's hereditary optic neuropathy. This case illustrates the difficulty physicians may encounter when trying to clinically differentiate Leber's from dominant optic atrophy in patients with remote visual loss, and it emphasizes the importance of obtaining a molecular assay for a mitochondrial mutation in cases of ambiguously classified hereditary optic neuropathy.

Adult↗
PubMed1991

Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis.

Retinitis pigmentosa (RP) is a group of disorders characterized by progressive degeneration of the outer retina, resulting in night blindness, visual field loss, an abnormal electroretinogram, and characteristic retinal pigmentary changes. An important step in the understanding of RP has been the recognition that some cases of autosomal dominant RP (ADRP) are caused by mutations in the rhodopsin gene. Multiple different point mutations within the coding sequence of the rhodopsin gene have been associated with ADRP. We have developed a GC-clamped denaturing-gradient-gel electrophoresis (DGGE) assay for the coding region of the rhodopsin gene and have used this assay to screen ADRP patients for mutations. The assay consists of amplifying with PCR the five exons of the rhodopsin gene and then analyzing each PCR product by DGGE. We have used this assay to detect three previously unreported rhodopsin base substitutions associated with ADRP. The use of this assay to identify ADRP patients who have various rhodopsin mutations has allowed us to begin studies seeking to correlate molecular genotype with clinical phenotype. Furthermore, GC-clamped DGGE has allowed us to identify families with ADRP not caused by a rhodopsin mutation. Such families will be important in the search for other genes involved in ADRP.

Amino Acid Sequence↗
PubMed1990

Mae III positively detects the mitochondrial mutation associated with type I Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy is a blinding disease that usually causes acute or subacute central visual loss in adolescent and young adult males. In patients who lack a family history of a similar illness, Leber's disease has been a diagnosis of exclusion. The recent discovery of a specific mitochondrial mutation in many pedigrees affected with the disease has provided the basis for rapid molecular diagnosis of one genetic type of Leber's disease. We have developed a new method, based on a Mae III (Boehringer Mannheim Biochemicals, Indianapolis, Ind) restriction fragment length polymorphism, for detecting the Wallace-type Leber's mutation. The method has several advantages over the previously used SfaN I method that make it more suitable for use as a general laboratory test. We demonstrate the utility of this new test in the diagnosis of Leber's disease in a patient with no family history of visual loss.

Adult↗
PubMed1990

Autosomal dominant neovascular inflammatory vitreoretinopathy.

Twenty-eight of 61 members of a six-generation family are affected by an autosomal dominant eye disease which has not been described previously. Affected patients are asymptomatic in early adulthood, but have vitreous cells and the selective loss of the b-wave on the electroretinogram. Later, peripheral retinal scarring and pigmentation, peripheral arteriolar closure, and neovascularization of the peripheral retina at the ora serrata or occasionally neovascularization of the optic disc develop. Cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma can cause profound visual loss. Vitrectomy reduces traction on the retina and allows for retinal reattachment. The role of argon laser photocoagulation or cryopexy in reducing the neovascular complications remains uncertain.

Adult↗
PubMed1990

The pathology of posterior amorphous corneal dystrophy.

The youngest affected member of a family with a five-generation history of posterior amorphous corneal dystrophy underwent penetrating keratoplasty. The corneal button was studied by light and electron microscopy, representing the first pathologic description of this condition. Light microscopy demonstrated fracturing of the most posterior collagen layers of the stroma and focal attenuation of endothelial cells. Electron microscopy showed the collagen fibers in the most posterior stromal lamellae to be disorganized. Descemet's layer was interrupted by a band of collagen fibers resembling stroma, and there was loss of endothelial cells. These findings suggest a developmental abnormality in the formation of the posterior stroma and Descemet's membrane in posterior amorphous corneal dystrophy.

Child, Preschool↗
PubMed1990

Optic nerve sheath distention in Leber's optic neuropathy and the significance of the "Wallace mutation".

We recently encountered a 27-year-old man who presented an atypical clinical picture of Leber's hereditary optic neuropathy: His family history was negative, visual loss continued steadily for over 8 months, circumpapillary microangiopathy was equivocal, the optic discs showed large physiologic cups, and both optic nerve sheaths were notably distended with increased subarachnoid fluid. The latter was confirmed by ultrasonography, computed tomography, and magnetic resonance imaging. The patient's asymptomatic brother also showed unimpressive circumpapillary microangiopathy in the fundi. The asymptomatic mother from France was then seen, and she showed classic circumpapillary microangiopathy in the fundi. Studies of mitochondrial DNA showed the classic point mutation at position 11778 as reported by Wallace in all three family members. Another patient previously seen with classic Leber's hereditary optic neuropathy recently had mitochondrial DNA studies along with three other affected family members and five unaffected family members in the maternal lineage. All nine of these individuals were completely normal at the Wallace locus. In fact, sequencing of the entire ND-4 gene from one affected individual revealed it to be perfectly normal at the amino acid level. The importance of obtaining quantitative ultrasonography and the 30 degrees test, and studying mitochondrial DNA in patients suspected of having Leber's optic nerve disease is emphasized.

Adult↗
PubMed1990

Best's vitelliform dystrophy.

Best's vitelliform dystrophy is an autosomal dominant disease that pathologically affects the retinal pigment epithelium and symmetrically affects the macula of patients at a very young age. Visual acuity tends to remain quite good for long periods of time. In the later stages of the disease, atrophic changes of the retinal pigment epithelium or scarring secondary to subretinal neovascular membranes with hemorrhage may cause a loss of central visual acuity. An abnormal diminished light to dark ratio of the electrooculogram is the hallmark of the disease. No other significant ocular abnormalities or systemic problems have been associated with this genetic disorder. No therapy exists for halting the progression of the disease with the possible exception of laser photocoagulation treatment used to ablate subretinal neovascular membranes in an attempt to avoid complications of subretinal hemorrhages. However, an accurate diagnosis and pedigree analysis is important for allowing the physician to perform adequate family and genetic counseling to affected patients.

Electrooculography↗
PubMed1985

Complete sequence of the chicken glyceraldehyde-3-phosphate dehydrogenase gene.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an evolutionarily conserved glycolytic enzyme, is constitutively expressed in most cell types yet is induced to high levels during the development of fast twitch muscle fibers. To analyze the organization and regulation of the chicken GAPDH gene, we first constructed a nearly full-length GAPDH cDNA clone (pGAD-28). pGAD-28 was used in the current study to screen a genomic library, and several overlapping clones were selected. The GAPDH coding region was detected within a 4.65-kilobase Xho I/EcoRI genomic fragment that was completely sequenced by using the M13 cloning vector system. A small portion of pGAD-28 was used as a primer to extend a 33-nucleotide sequence from the 5' end of GAPDH mRNA. The canonical promoter "TATA" region was found 22 base pairs from the 5' end of the mRNA. The 5' end of the GAPDH gene is extraordinarily G+C-rich (80%) and contains two inverted sequences with a 9-base-pair homology found at -58 (G-G-G-G-C-G-G-G-C) and -93 (G-C-C-C-G-C-C-C-C) nucleotides from the transcription start site. Sequencing also revealed the location of 11 introns within the transcribed portion of the GAPDH gene. The placement of at least 3 of the introns corresponds to the boundaries of protein domains within prokaryotic and eukaryotic GAPDHs that were previously detected by x-ray crystallography. This concordance suggests that introns may have participated in the construction of the earliest GAPDH gene.

Animals↗
PubMed1983

Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was purified from the breast muscles of 3-week-old chickens and used to raise a specific antiserum in rabbits. This antiserum was coupled to an in vitro translation assay to monitor the purification of GAPDH mRNA. RNA was isolated from identical breast muscles and consecutively fractionated with several techniques to yield a preparation of GAPDH mRNA which was at least 50% pure. Double-stranded cDNA was made against this purified RNA, inserted into pBR322, and used to transform Escherichia coli. Recombinants were screened by colony filter hybridization with a cDNA probe made against the purified RNA. The hybridization-positive clone with the largest insert, pGAD-28, was then characterized by using pGAD-28-cellulose to select complementary RNA from total poly(A) RNA and then translating the hybridization-selected RNA in vitro. The single translation product was shown to be GAPDH by (1) comigration with pure GAPDH on sodium dodecyl sulfate-polyacrylamide gels, (2) precipitation with specific anti-GAPDH antiserum, (3) cyanylation fingerprinting, and (4) AMP-agarose affinity chromatography. pGAD-28 was mapped with several restriction enzymes and then sequenced by the method of Maxam and Gilbert [Maxam, A. M., & Gilbert, W. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 560]. The 1261-nucleotide insert was found to contain 29 nucleotides of noncoding sequence at the 5' end, the entire coding region, and 230 nucleotides of the 3'-noncoding region including a poly(A) addition signal (AATAAA) and the first five residues of the poly(A) tail.

Animals↗
PubMedDate not supplied

Autosomal dominant Stargardt-like macular dystrophy.

Autosomal dominant Stargardt-like macular dystrophy is one of the early onset macular dystrophies. It is characterized clinically in its early stages by visual loss and by the presence of atrophic macular changes with or without the presence of yellowish flecks. It is an important retinal dystrophy to study, not only because it has implications in the care and treatment of patients with the condition, but because it also provides important information regarding retinal function. Review of the literature suggests that many of the reported families are linked to chromosome 6q. Genetic and genealogical evidence suggests that these families have descended from a common ancestor or founder. The recent identification of a disease-causing gene that is involved in fatty acid metabolism may have implications in the study of the more common age-related macular degeneration. We review the recent clinical, genetic, and genealogical aspects of autosomal dominant Stargardt-like macular dystrophy.

Chromosomes, Human, Pair 6↗