Localization of the gene for rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration to chromosome 17q21.

Rapidly progressive autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration (PPND) is a neurodegenerative disorder which begins later in life (> 30 years of age) and is characterized by rapidly progressive parkinsonism, dystonia, dementia, perservative vocalizations and pyramidal tract dysfunction. The disease is observed in a large American family that includes almost 300 members in nine generations with 34 affected individuals. In this kindred evidence for linkage to chromosome 17q21 was obtained with a maximum lod score of 9.

Is there a genetic susceptibility to idiopathic parkinsonism?

The search for the etiology of idiopathic parkinsonism (IP) has been difficult and largely unsuccessful. Recently, there has been renewed interest in the possibility that there are genetic susceptibility loci for IP. Part of this interest has been spurred by recent advances in molecular genetics.

A high-resolution genetic linkage map of the pericentromeric region of the human X chromosome.

We generated a high-resolution genetic linkage map of the pericentromeric region of the human X chromosome from approximately Xp11.4 to Xq22. This map contains 41 loci defined by 50 marker systems genotyped in the CEPH families.

Localization of disinhibition-dementia-parkinsonism-amyotrophy complex to 17q21-22.

Disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) is defined by familial adult-onset behavioral disturbance, followed by frontal lobe dementia, parkinsonism, and amyotrophy in variable proportions. A genetic etiology of DDPAC was suspected because of the familial clustering in family Mo, despite their wide geographic distribution. We have mapped the DDPAC locus to a 12-cM (sex averaged) region between D17S800 and D17S787 on chromosome 17q21-22.

Exclusion of the DYT1 locus in a non-Jewish family with early-onset dystonia.

The DYT1 gene on chromosome 9q34 underlies idiopathic torsion dystonia (ITD) in Jewish and non-Jewish families with childhood and adolescent-onset dystonia that usually starts in a limb, spreads to other limbs, and uncommonly involves cranial muscles. We examined 39 members of a Mennonite family of German ancestry in which seven were affected with ITD. Age at onset was 14.

Turcot's syndrome: evidence for linkage to the adenomatous polyposis coli (APC) locus.

Objective: To investigate the possibility that neuroepithelial tumors in Turcot's syndrome are caused by pleiotropic mutations in the gene for adenomatous polyposis coli (APC), a tumor-suppressor gene implicated in colonic cancer.

Methods: We studied the inheritance patterns of genetic markers for the chromosome 5q21 region in 12 members of a Turcot's syndrome kindred with five affected members. We performed linkage analysis to detect linkage between the disease phenotype and DNA markers.

Adductor laryngeal breathing dystonia in a patient with lubag (X-linked dystonia-Parkinsonism syndrome).

We report a patient with Lubag (X-linked dystonia-parkinsonism) who presented with severe respiratory stridor from adductor laryngeal breathing dystonia. Emergency tracheostomy was necessary, and subsequent laryngeal injection with botulinum toxin led to worsening aspiration. Botulinum toxin injection for severe lingual dystonia was successful.

Linkage mapping of dopa-responsive dystonia (DRD) to chromosome 14q.

Dopa-responsive dystonia (DRD) is an autosomal-dominant neurological disorder which appears to result from a genetically determined deficiency of striatal dopamine. Pathological evidence suggests that this may be due to the establishment of a reduced number of dopaminergic nerve terminals in the striatum, or to an excessive reduction (pruning) of these terminals in early development. We have mapped the DRD gene to chromosome 14 by linkage analysis in 3 families with a maximum 2-point lod score of 4.

Phenotypic expression of X-linked dystonia-parkinsonism (lubag) in two women.

Lubag (X-linked dystonia-parkinsonism) has been considered a sex-linked recessive trait and has been mapped to the pericentromeric region of the X chromosome. We studied a 54-year-old man with lubag and two of his female first cousins. Genetic typing was carried out using X chromosome markers.

Positron emission tomographic findings in Filipino X-linked dystonia-parkinsonism.

Regional and global metabolic rates for glucose (rCMRGlc and GMR) were estimated using [18F]fluorodeoxyglucose and positron emission tomography in 3 patients with Filipino X-linked dystonia-parkinsonism (lubag). In all 3 patients a selective reduction in normalized striatal glucose metabolism (rCMRGlc/GMR) was observed compared with 15 normal volunteer subjects. Presynaptic nigrostriatal function was assessed in these patients using [18F]fluorodopa and positron emission tomography.

Spinal muscular atrophy is not the result of mutations at the beta-hexosaminidase or GM2-activator locus.

The disease locus for the clinically heterogeneous childhood spinal muscular atrophies (SMA) maps to the chromosome 5 subregion, 5q11.2-13.3.

Genetic mapping of "Lubag" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.

"Lubag" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. We have established linkage between the disease phenotype "lubag" and DNA markers which span the Xp11.22-Xq21.

Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3.

SPINAL muscular atrophy (SMA) describes a group of heritable degenerative diseases that selectively affect the alpha-motor neuron. Childhood-onset SMAs rank second in frequency to cystic fibrosis among autosomal recessive disorders, and are the leading cause of heritable infant mortality. Predictions that genetic heterogeneity underlies the differences between types of SMA, together with the aggressive nature of the most-severe infantile form, make linkage analysis of SMA potentially complex.

Nucleic acid sequences of the oncogene v-rel in reticuloendotheliosis virus strain T and its cellular homolog, the proto-oncogene c-rel.

Reticuloendotheliosis virus strain T (Rev-T) is a highly oncogenic replication-defective retrovirus which contains the oncogene v-rel. It is thought that Rev-T arose when a virus similar to Rev-A, the helper virus of Rev-T, infected a turkey and recombined with c-rel from that turkey. There is one large c-rel locus in the turkey genome which contains all of the sequences homologous to v-rel (K.

Structure and dimorphism of c-rel (turkey), the cellular homolog to the oncogene of reticuloendotheliosis virus strain T.

A locus has been identified in turkey DNA that contains nucleotide sequences homologous to the oncogene (v-rel) in the avian retrovirus, reticuloendotheliosis virus strain T. This locus, c-rel, has been molecularly cloned from an apparently heterozygous turkey. c-rel is approximately 23 kilobase pairs in length, with at least seven apparent introns, and contains sequences sufficient to account for all of v-rel.

The organization of c-rel in chicken and turkey DNAS.

The process of transduction of a proto-oncogene involves the loss of intervening sequences, the loss of 3' mRNA terminal sequences, and possible base changes. It is not possible to know how similar the c-rel sequences we studied are to sequences from which v-rel arose. If one of the alleles we studied is identical to progenitor sequences of v-rel, then base changes must have occurred during the process of transduction.

Structure and expression of c-rel, the cellular homolog to the oncogene of reticuloendotheliosis virus strain T.

The cellular homolog of the onc sequences in the avian retrovirus reticuloendotheliosis virus strain T (v-rel) was studied by molecular cloning and nucleic acid hybridization. In contrast to v-rel sequences, which are 1.4 kilobase pairs long, the cellular homolog, c-rel, from line 15B chickens is at least 25 kilobase pairs long, with multiple apparent introns.

The virus-specific intracellular RNA species of two murine coronaviruses: MHV-a59 and MHV-JHM.

Seven virus-specific, polyadenylated RNA species have been identified in mouse cells infected with the murine coronaviruses MHV-A59 (A59V) or MHV-JHM (JHMV). MHV-infected 17CL·1 cells were labeled with [P]orthophosphate in the presence of actinomycin D and the cytoplasmic RNA was extracted and analyzed by agarose gel electrophoresis. These RNA species range in size from 6.

The replication of murine coronaviruses in enucleated cells.

Coronaviruses JHMV and A59V have been shown to replicate, produce viral-specific antigens and cytopathic effects (CPE) in enucleated 17CL-1 cells.