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Biomedical subjects

E M Stone

Publications and source records attributed to E M Stone.

At least 145 records · Page 8Linked to original sources
PubMed1993

Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene.

Butterfly-shaped pigment dystrophy of the fovea is an autosomal dominant eye disease characterized by a bilateral accumulation of yellowish or pigmented material at the level of the retinal pigment epithelium. It shares some clinical and histopathologic features with age related macular degeneration which is the most common cause of legal blindness in older patients. We screened affected patients from a three generation family with butterfly dystrophy for mutations in candidate genes. A base substitution was identified in the peripherin (RDS) gene and DNA sequencing revealed a G to A transition in codon 167 that substitutes aspartic acid for a highly conserved glycine. The mutation segregates with the disease phenotype (Zmax = 4, theta = 0) strongly suggesting that it causes the macular disease in this family.

Adult↗
PubMed1993

Genetic linkage of familial open angle glaucoma to chromosome 1q21-q31.

Glaucoma is a significant cause of blindness world wide. There is evidence to suggest that at least a subset of the disease is determined genetically. We studied 37 members of a family affected with an autosomal dominant form of juvenile open angle glaucoma and 22 were found to be affected. Linkage analysis using short tandem repeat markers mapped the disease-causing gene to chromosome 1q21-q31. Eight markers were significantly linked (Zmax > 3.0) to the disease, with the highest lod score 6.5 (theta = 0), provided by D1S212. The atrial natriuretic peptide (ANP)/receptor system has been proposed to have a role in glaucoma and one of the ANP receptor genes maps to chromosome 1q.

Chromosome Mapping↗
PubMed1993

Linkage of Bardet-Biedl syndrome to chromosome 16q and evidence for non-allelic genetic heterogeneity.

Bardet-Biedl syndrome is an autosomal recessive disorder characterized by mental retardation, obesity, retinitis pigmentosa, polydactyly and hypogonadism. Other findings include hypertension, diabetes mellitus and renal and cardiovascular anomalies. We have performed a genome-wide search for linkage in a large inbred Bedouin family. Pairwise analysis established linkage with the locus D16S408 with no recombination and a lod score of 4.2. A multilocus lod score of 5.3 was observed. By demonstrating homozygosity, in all affected individuals, for the same allele of marker D16S408, further support for linkage is found, and the utility of homozygosity mapping using inbred families is demonstrated. In a second family, linkage was excluded at this locus, suggesting non-allelic genetic heterogeneity in this disorder.

Chromosome Mapping↗
PubMed1993

A user-friendly Hypercard interface for human linkage analysis.

The availability of a large number of highly informative genetic markers has made human linkage analysis faster and easier to perform. However, current linkage analysis software does not provide an organizational database into which a large body of linkage data can be easily stored and manipulated. This manual entry and editing of linkage data is often time consuming and prone to typing errors. In addition, the large number of alleles in many of these markers must be reduced in order to perform linkage analysis with multiple loci across large genetic distances. This reduction in allele number is often difficult and confusing, especially in large pedigrees. We have taken advantage of the Macintosh-based Hypercard program to develop an interface with which linkage data can be easily stored, retrieved and edited. For each family, the components of the pedigree, including ID numbers, sex and affection status, only need to be entered once. The program (Linkage Interface) retrieves this information each time the data from a new polymorphic marker is entered. Linkage Interface has flexible editing capabilities that allow the user to change any portion of the pedigree, including the addition or deletion of family members, without affecting previously entered genotype data. Linkage Interface can also analyze both the pedigree and marker data and will detect any inconsistencies in inheritance patterns. In addition, the program can reduce the number of alleles for a polymorphic marker. Linkage Interface will then compare the 'reduced' data to the original marker data and assists in maintaining all informative meioses by pointing out which meioses have become non-informative.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1993

Vietnamese infant and childhood mortality in relation to the Vietnam War.

OBJECTIVES: There is obvious potential for war to adversely affect infant and childhood mortality through direct trauma and disruption of the societal infrastructure. This study examined trends in Vietnam through the period of the war. METHODS: The 1988 Vietnam Demographic and Health Survey collected data on reproductive history and family planning from 4172 women aged 15 through 49 years in 12 selected provinces of Vietnam. The 13,137 births and 737 deaths to children younger than age 6 reported by the respondents were analyzed. RESULTS: For the country as a whole, infant and childhood mortality dropped by 30% to 80% from the prewar period to the wartime period and was stable thereafter. In provinces in which the war was most intense, mortality did not decline from the prewar period to the wartime period but declined after the war, consistent with an adverse effect during the wartime period. CONCLUSIONS: The data are limited by assignment of birth location on the basis of mother's current residence and by inadequate information on areas of war activity. Nonetheless, the data do not indicate a widespread, sizable adverse effect of the war on national infant and childhood mortality in Vietnam but suggest detrimental effects in selected provinces.

Adult↗
PubMed1992

Ocular findings associated with rhodopsin gene codon 17 and codon 182 transition mutations in dominant retinitis pigmentosa.

Six members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine transition mutation in the second nucleotide of codon 17 in the rhodopsin gene that resulted in a threonine to methionine change. Three members from another family with autosomal dominant retinitis pigmentosa showed a guanine-to-adenine transition mutation in the first nucleotide of codon 182 in the rhodopsin gene that resulted in a glycine to serine change. Each of these two mutations presented with a similar phenotype because both showed a regional predilection for pigmentary changes to occur in the inferior part of the retina as well as field impairment predominantly in the superior hemisphere. Electroretinographic amplitudes were more substantial than usually encountered in other forms of retinitis pigmentosa, a finding consistent with the better visual prognosis in patients with either of these two mutations. This article documents the association of two similar phenotypes of autosomal dominant retinitis pigmentosa with specific gene defects at a molecular level.

Adolescent↗
PubMed1992

Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa.

Three members of one family and one person from another family were found to have a guanine-to-adenine transition mutation in the first nucleotide of codon 106 in the rhodopsin gene that results in a glycine-to-arginine change. All affected members presented with a similar phenotype that included a regional predilection for pigmentary changes to occur in the inferior retina as well as visual field impairment predominantly in the superior hemisphere. The distribution of pigmentary changes, pattern of visual field loss, and substantial remaining electroretinographic amplitudes with normal implicit times were consistent with a form of "sector" retinitis pigmentosa. We documented the association of a distinct phenotype of autosomal dominant retinitis pigmentosa with a better visual prognosis and a specific rhodopsin gene mutation.

Adult↗
PubMed1992

Ocular findings associated with rhodopsin gene codon 267 and codon 190 mutations in dominant retinitis pigmentosa.

Two members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine mutation in the second nucleotide of codon 267 in the rhodopsin gene that resulted in a proline-to-leucine change. Two members of another family with autosomal dominant retinitis pigmentosa showed a guanine-to-thymine mutation in the first nucleotide of codon 190 in the rhodopsin gene that resulted in an aspartate-to-tyrosine change. Three members from a third family with autosomal dominant retinitis pigmentosa were also found to have a mutation in codon 190; however, this guanine-to-adenine mutation in the first nucleotide of codon 190 resulted in an aspartate-to-asparagine change. The relatively less severe functional retinal impairment in our patients with a transmembrane codon 267 rhodopsin gene mutation is generally comparable with that observed in a previously described codon 58 transmembrane mutation. The two families with different intradiscal codon 190 mutations showed a considerable difference in severity of their disease.

Adult↗
PubMed1992

Procollagen II gene mutation in Stickler syndrome.

Four affected members of a family with Stickler syndrome were found to have a single base-pair deletion resulting in a translational frameshift in exon 40 of the procollagen II (COL2A1) gene on chromosome 12. This mutation was not seen in any of five clinically unaffected family members or in any of 15 unrelated control patients. All affected members had distinctly abnormal vitreous syneresis and all had retinal perivascular pigmentation. Retinal detachments occurred in three of the four affected patients. Three of the four affected patients had peripheral cortical "wedge" cataracts, and the fourth had extensive nuclear sclerosis. Abnormalities of the soft palate were found in all four affected patients. All patients reported severe joint pains, and epiphyseal dysplasia was found radiographically in all patients.

Adolescent↗
PubMed1992

Protein phosphatases and cell division cycle control.

Fission yeast has at least ten protein phosphatase genes that appear to play distinct roles in cell cycle control. Because of functional overlap, a clear lethal phenotype can be obtained only after multiple genetic alterations. Cells that have lost the protein phosphatase 1 (PP1)-like dis2/sds21 phosphatase activities prematurely enter mitosis and remain in a defective mitotic state with high H1 kinase activity and without sister chromatid disjunction. The same phenotype can be obtained in the presence of hydroxyurea. Overexpression of PP1-like phosphatase, on the other hand, delays the entry into mitosis. Cells that have lost PP2A-like ppa2 phosphatase activity also prematurely enter mitosis with a reduction in cell size. This semi-wee phenotype is enhanced in delta ppa2 mutants treated with the phosphatase inhibitor, okadaic acid. Genetic interactions between ppa2 and mitotic regulators suggest that ppa1/ppa2 phosphatase may directly or indirectly inhibit p34cdc2/cyclin kinase. Thus both PP1- and PP2A-like phosphatases in fission yeast may negatively regulate entry into mitosis. The major property of the dis2/sds21 mutant which is distinct from those of the ppa2/ppa1 mutant is its failure to inactivate the p34cdc2/cyclin complex after entry into mitosis. A novel phosphatase regulator encoded by sds22+ binds to dis2 phosphatase and controls the substrate specificity which appears to become essential in the progression from metaphase to anaphase.

Cell Division↗
PubMed1992

Avellino corneal dystrophy. Clinical manifestations and natural history.

PURPOSE: The pathologic features of a variant of granular corneal dystrophy has been described in which the presence of lattice changes in addition to characteristic granular lesions has been documented. The authors investigated the mode of inheritance, natural history, and clinical manifestations of this dystrophy. METHODS: A family with this condition was investigated, and a pedigree was established. Family members underwent ophthalmic examination, and ophthalmic history was obtained. In addition, pathologic examination of corneal tissue from affected patients was performed. RESULTS: Similar to the four previously described cases, this family also traced its origins to Avellino, Italy. This autosomal dominant condition affected 27 of 92 family members, ranging in age from 5 to 77 years. Granular deposits were the earliest and most common manifestations. Lattice lesions were present in some patients with granular lesions. Older patients had anterior stromal haze between deposits, which impaired visual acuity. Recurrent granular deposits were noted in donor corneal tissue after penetrating keratoplasty for this condition. Pathologic examination of corneal tissue from affected patients confirmed the presence of hyaline material seen in granular dystrophy as well as fusiform deposits of amyloid, similar to those seen in lattice dystrophy type I. CONCLUSION: This study establishes the natural history and clinical manifestations of this condition.

Adolescent↗
PubMed1992

Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13.

Macular degeneration is the most common cause of legal blindness in older patients in developed countries. Best's vitelliform dystrophy is an early-onset, autosomal dominant form of macular degeneration characterized by an egg-yolk-like collection of lipofuscin beneath the pigment epithelium of the retinal macula. Fifty-seven members of a five-generation family affected with this disease were studied. A combination of ophthalmoscopy and electro-oculography was used for diagnosis; 29 patients were found to be affected and 16 unaffected. Linkage analysis mapped the disease-causing gene to chromosome 11q13. Three markers in this region were found to be significantly linked (Zmax > 3.0) to the disease. Multipoint analysis yielded a maximum Lod score of 9.3 in the interval between markers INT2 and D11S871.

Chromosome Mapping↗
PubMed1992

Genetic linkage of autosomal dominant neovascular inflammatory vitreoretinopathy to chromosome 11q13.

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an inherited eye disease characterized by retinal and iris neovascularization, abnormal retinal pigmentation, anterior chamber and vitreous inflammation, cystoid macular edema, vitreous hemorrhage, and traction retinal detachment. Some of these clinical features are shared by more common, potentially blinding, conditions including diabetic retinopathy, uveitis, and retinitis pigmentosa. Elucidation of the molecular pathogenesis of ADNIV has the potential to provide insight into the mechanisms of these common disorders. One hundred and sixteen members of an eight generation family affected with ADNIV were examined. A combination of slit lamp biomicroscopy, ophthalmoscopy, and electroretinography was used to establish the diagnosis and 34 family members were found to be affected. Blood samples were obtained from thirty-three of these individuals and nine spouses and used for chromosome linkage analysis with denaturing gradient gel and short tandem repeat polymorphisms. Two markers that map to chromosome 11q13 were found to be significantly linked to the ADNIV phenotype. There were no recombinants between the disease phenotype and marker D11S527 and multipoint analysis yielded a maximum LOD score of 11.9 centered on this marker.

Adult↗
PubMed1992

Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation.

Five patients with Leber's hereditary optic neuropathy (LHON) and the 11778 mitochondrial mutation spontaneously recovered 20/40 or better visual acuity in at least one eye after months to years of legal blindness. The patients ranged in age from 9 to 45 years, and the duration of visual loss before recovery ranged from several months to 5.9 years. These patients constitute only about 4% of the 136 affected LHON patients we have studied who also had the 11778 mutation in their mitochondrial DNA. Thus, even though the visual prognosis for most patients with LHON and the 11778 mutation is poor, a few individuals do recover near-normal vision in at least one eye even years after the initial visual loss.

Adolescent↗
PubMed1992

Detection of multiallele polymorphisms within gene sequences by GC-clamped denaturing gradient gel electrophoresis.

The ability to efficiently detect DNA polymorphisms is essential for the completion of a high-resolution polymorphic linkage map of the human genome. Currently the most informative polymorphisms are the multiallelic dinucleotide repeat polymorphisms. However, many gene sequences lack an associated dinucleotide repeat sequence. We used GC-clamped denaturing gradient gel electrophoresis to screen for DNA polymorphisms in the following six gene sequences: MCC, p53, prealbumin (transthyretin), rhodopsin, S-antigen, and TGF-alpha. A single-base sequence polymorphism was identified in each of these gene sequences. Some of these polymorphisms were multiallelic and highly informative. Our results demonstrate the value of denaturing gradient gel electrophoresis for both identifying and analyzing human DNA polymorphisms. The ability to detect highly informative polymorphisms within gene sequences will greatly contribute to a gene-based polymorphic linkage map.

Alleles↗