Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Mihael H. Polymeropoulos is active.

Publication


Featured researches published by Mihael H. Polymeropoulos.


Nature | 1998

The ubiquitin pathway in Parkinson's disease

Elisabeth Leroy; Rebecca Boyer; Georg Auburger; Barbara Leube; Gudrun Ulm; Eva Mezey; Gyongyi Harta; Michael J. Brownstein; Sobhanadditya Jonnalagada; Tanya Chernova; Anindya Dehejia; Christian Lavedan; Thomas Gasser; Peter J. Steinbach; Keith D. Wilkinson; Mihael H. Polymeropoulos

Mutations of the α-synuclein gene, have been identified in some familial forms of Parkinsons disease, and α-synuclein protein has been shown to accumulate in the brains of patients with the disease. These findings suggest that Parkinsons disease may be caused by the abnormal aggregation of α-synuclein protein. Here we have identified in a German family with Parkinsons disease a missense mutation in the ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) gene. We show that this mutation, Ile93Met, causes a partial loss of the catalytic activity of this thiol protease, which could lead to aberrations in the proteolytic pathway and aggregation of proteins.


Science | 1996

Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

Mihael H. Polymeropoulos; Joseph J. Higgins; Lawrence I. Golbe; William G. Johnson; Susan E. Ide; Giuseppe Di Iorio; G. Sanges; Edward S. Stenroos; Lana T. Pho; Alejandro A. Schäffer; Alice Lazzarini; Robert L. Nussbaum; Roger C. Duvoisin

Parkinsons disease (PD) is the second most common neurodegenerative disorder after Alzheimers disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.


Nature Genetics | 2000

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis

Victor L. Ruiz-Perez; Susan E. Ide; Tim M. Strom; Bettina Lorenz; David I. Wilson; Kathryn Woods; Lynn Mertens King; Clair A. Francomano; Peter Freisinger; Stephanie Spranger; Bruno Marino; Bruno Dallapiccola; Michael Wright; Thomas Meitinger; Mihael H. Polymeropoulos; Judith A. Goodship

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992–amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.


Nucleic Acids Research | 1991

Dinucleotide repeat polymorphism at the human non-histone chromosomal protein HMG14 gene

Mihael H. Polymeropoulos; Hong Xiao; D.S. Rath; Carl R. Merril

References: 1) Kobayashi.K. et al. (1988) J. Biochem. 103, 907-912. 2) Weber,J.L. and May,P.E. (1989) Am. J. Hum. Genet. 44, 388-3%. 3)Jumen,C. and McBride.O.W. (1989) Cytogenet. Cell Genet. 51, 226-258. 4) Weber.J.L. etal. (1990) Nucl. Acids Res. 18, 4637. Source/Description: The polymorphic (GT)n repeat begins at base pair 4829 in intron E of the human non-histone chromosomal protein HMG14 gene on chromosome 21q22.3 (1). The polymorphism can be typed using the polymerase chain reaction (PCR) as described previously (2). The predicted length of the amplified sequence was 82 bp.


American Journal of Human Genetics | 1999

Clinical and Molecular Genetic Analysis of 19 Wolfram Syndrome Kindreds Demonstrating a Wide Spectrum of Mutations in WFS1

Carol Hardy; Farhat L. Khanim; Rosarelis Torres; Martin Scott-Brown; Anneke Seller; Joanna Poulton; David A. Collier; Jeremy Kirk; Mihael H. Polymeropoulos; Farida Latif; Timothy Barrett

Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and progressive optic atrophy. mtDNA deletions have been described, and a gene (WFS1) recently has been identified, on chromosome 4p16, encoding a predicted 890 amino acid transmembrane protein. Direct DNA sequencing was done to screen the entire coding region of the WFS1 gene in 30 patients from 19 British kindreds with Wolfram syndrome. DNA was also screened for structural rearrangements (deletions and duplications) and point mutations in mtDNA. No pathogenic mtDNA mutations were found in our cohort. We identified 24 mutations in the WFS1 gene: 8 nonsense mutations, 8 missense mutations, 3 in-frame deletions, 1 in-frame insertion, and 4 frameshift mutations. Of these, 23 were novel mutations, and most occurred in exon 8. The majority of patients were compound heterozygotes for two mutations, and there was no common founder mutation. The data were also analyzed for genotype-phenotype relationships. Although some interesting cases were noted, consideration of the small sample size and frequency of each mutation indicated no clear-cut correlations between any of the observed mutations and disease severity. There were no obvious mutation hot spots or clusters. Hence, molecular screening for Wolfram syndrome in affected families and for Wolfram syndrome-carrier status in subjects with psychiatric disorders or diabetes mellitus will require complete analysis of exon 8 and upstream exons.


Journal of Clinical Investigation | 1998

Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21.

Shailendra B. Patel; Gerald Salen; Hideki Hidaka; Peter O. Kwiterovich; Anton F. H. Stalenhoef; Tatu A. Miettinen; Scott M. Grundy; Mi-Hye Lee; Jeffrey Rubenstein; Mihael H. Polymeropoulos; Michael J. Brownstein

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the bodys ability to selectively exclude other dietary sterols are poorly understood. Studies of the rare autosomal recessively inherited disease sitosterolemia (OMIM 210250) may shed some light on these processes. Patients suffering from this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the livers ability to preferentially and rapidly excrete these non-cholesterol sterols into bile. Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to an advancement in the management of this important cardiovascular risk factor. By studying 10 well-characterized families with this disorder, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0).


Neuroreport | 2000

Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients.

Philip Wintermeyer; Rejko Krüger; Wilfried Kuhn; Thomas J. J. Müller; Dirk Woitalla; Daniela Berg; Georg Becker; Elisabeth Leroy; Mihael H. Polymeropoulos; Klaus Berger; H. Przuntek; Ludger Schöls; Jörg T. Epplen; Olaf Riess

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinsons disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36–0.88; p = 0.012, pc = 0.047, χ2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration.


Human Genetics | 1998

Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson’s disease

Elisabeth Leroy; Dimitri Anastasopoulos; Spiridon Konitsiotis; Christian Lavedan; Mihael H. Polymeropoulos

Abstract Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and is manifested as a movement disorder. A positive family history is the second most important risk factor for developing the illness, after age. Both autosomal dominant and recessive forms of the illness have been described. Recently deletions in a novel gene, parkin, have been associated with the autosomal recessive form of the illness in Japanese families. In this study, we demonstrate that deletions of exons 5, 6 and 7 of the parkin gene are present in two affected individuals of a Greek pedigree with early onset Parkinson’s disease. However, no deletions were identified in a different branch of the same pedigree with three affected individuals. These results suggest that deletions in the parkin gene will be found in other families besides those of Japanese origin and that there must be at least one additional locus responsible for early onset autosomal recessive Parkinson’s disease.


Molecular Psychiatry | 2009

Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study.

Christian Lavedan; Louis Licamele; Simona Volpi; Jennifer Hamilton; Callie Michelle Heaton; Kendra Tomino Mack; Rebecca Lannan; A Thompson; Curt D. Wolfgang; Mihael H. Polymeropoulos

A whole genome association study was performed in a phase 3 clinical trial conducted to evaluate a novel antipsychotic, iloperidone, administered to treat patients with schizophrenia. Genotypes of 407 patients were analyzed for 334 563 single nucleotide polymorphisms (SNPs). SNPs associated with iloperidone efficacy were identified within the neuronal PAS domain protein 3 gene (NPAS3), close to a translocation breakpoint site previously observed in a family with schizophrenia. Five other loci were identified that include the XK, Kell blood group complex subunit-related family, member 4 gene (XKR4), the tenascin-R gene (TNR), the glutamate receptor, inotropic, AMPA 4 gene (GRIA4), the glial cell line-derived neurotrophic factor receptor-alpha2 gene (GFRA2), and the NUDT9P1 pseudogene located in the chromosomal region of the serotonin receptor 7 gene (HTR7). The study of these polymorphisms and genes may lead to a better understanding of the etiology of schizophrenia and of its treatment. These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio.


Molecular Psychiatry | 1998

Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease

Mezey E; Anindya Dehejia; Harta G; Tresser N; Sharon F. Suchy; Robert L. Nussbaum; Michael J. Brownstein; Mihael H. Polymeropoulos

A missense mutation in the human alpha synuclein gene was recently identified in some cases of familial Parkinsons disease (FPD). We have developed an antibody that recognizes the C-terminal 12 amino acids of the human alpha synuclein protein and have demonstrated that alpha synuclein is an abundant component of the Lewy bodies found within the degenerating neurons of patients with Parkinsons disease (PD). The presence of alpha synuclein in Lewy bodies of sporadic PD patients suggests a central role for alpha synuclein in the pathogenesis of PD.

Collaboration


Dive into the Mihael H. Polymeropoulos's collaboration.

Top Co-Authors

Avatar

Christian Lavedan

National Institutes of Health

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

D.S. Rath

St. Elizabeths Hospital

View shared research outputs
Top Co-Authors

Avatar

Hong Xiao

St. Elizabeths Hospital

View shared research outputs
Top Co-Authors

Avatar

Carl R. Merril

National Institutes of Health

View shared research outputs
Top Co-Authors

Avatar

Elisabeth Leroy

National Institutes of Health

View shared research outputs
Top Co-Authors

Avatar

Susan E. Ide

National Institutes of Health

View shared research outputs
Top Co-Authors

Avatar

Rosarelis Torres

George Washington University

View shared research outputs
Top Co-Authors

Avatar

Anindya Dehejia

National Institutes of Health

View shared research outputs
Researchain Logo
Decentralizing Knowledge