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P Propping

Publications and source records attributed to P Propping.

At least 145 records · Page 8Linked to original sources
PubMed1996

Efficacy and side-effects of clozapine: testing for association with allelic variation in the dopamine D4 receptor gene.

Genetic factors are supposed to play a major role not only in the etiology of psychiatric disorders but also in individual response to medications. To test the hypothesis that inter-individual differences in response to clozapine and the occurrence of side-effects might be influenced by variations in the dopamine D4 receptor gene, we examined frequencies of four known polymorphic sites affecting protein structure in the dopamine D4 receptor gene in 149 patients with schizophrenia or schizoaffective disorder treated with clozapine. The D4 polymorphisms included a 13-base pair deletion, which through a frameshift leads to a truncated nonfunctional receptor protein. There were, however, no significant differences in genotype counts between responders and nonresponders. Furthermore, no side-effect was found to be associated with genetic variants of the dopamine D4 receptor.

Adult↗
PubMed1996

Apolipoprotein E genotype distribution in schizophrenia.

We examined the hypothesis that apolipoprotein E (apoE) isoforms-besides their well-established role in the aetiology of early and late onset Alzheimer's disease (AD)-may be involved in the development of schizophrenia. We determined apoE genotypes in 98 schizophrenic patients and 98 sex and age matched controls. No significant difference in apoE allele frequencies were observed between schizophrenic patients, subpopulations of schizophrenics, or controls. There was also no difference in the mean age at onset depending on the number of apoE epsilon 4 alleles found in the patients. Our data do not support an association between AD and schizophrenia based on apoE acting as a common denominator in the pathogenesis of both diseases.

Adult↗
PubMed1996

[Genetic counseling in psychiatric diseases].

We review current knowledge and application of genetic counselling for psychiatric disorders. Empirical data for genetic counselling exist for affective disorder, schizophrenia, Alzheimer's and Huntington's disease. In Huntington's chorea and partly in Alzheimer's disease molecular genetic methodology may be applied, whereas for affective disorder and schizophrenia only empirical risk figures are available. We describe the principles of genetic counselling and their application in the respective diseases. Problems of presymptomatic testing are particularly outlined. In addition, teratogenic aspects of therapy with psychopharmacological agents during pregnancy are discussed.

Abnormalities, Drug-Induced↗
PubMed1996

Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease.

The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations.

Adolescent↗
PubMed1996

The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder.

In the present study, we evaluated the possible contribution of genetic variation of the serotonin 5-HT7 receptor to the development of schizophrenia and bipolar affective disorder. Cloning and characterization of exon-flanking intronic sequences enabled us to investigate the whole coding region and the exon-intron boundaries of the human 5-HT7 receptor gene. Using single-strand conformational analysis, we screened for presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic and 46 bipolar affective patients, as well as 46 healthy controls. We detected two rare naturally occurring receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotide substitution (A-->G) at position +1233. The occurrence of the Pro-279-Leu and Thr-92-Lys substitutions was studied in an extended sample of patients (n = 462) and controls (n = 335). The Leu-279 variant was found in similar frequency in all groups, indicating that presence of this variant is not causally related to the development of schizophrenia or bipolar affective disorder. The Lys-92 variant was found in a single individual who suffered from bipolar affective disorder. Investigation of the patient's family revealed independent segregation between the Lys-92 variant and psychiatric illness. Our data suggests that genetic variation of the 5-HT7 receptor does not play a major role in the development of bipolar affective disorder and schizophrenia.

Bipolar Disorder↗
PubMed1995

Human adenosine A1 receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 1q31-32.1 using a silent polymorphism in the coding region.

Adenosine is a major inhibitory neuromodulator in the central nervous system. One of the receptors mediating the central effects of adenosine is the adenosine A1 receptor. We performed a systematic mutation scan of the coding region of the adenosine A1 receptor gene to explore its variability in the general population. Investigating 40 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. We detected, however, a frequent T to G substitution at nucleotide position 716 which constitutes the first variant described in an adenosine receptor gene. It was used for fine scale linkage mapping of the A1 gene. Employing a polymerase-chain-reaction-based restriction assay, we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor in a gene cluster around the renin gene on chromosome 1q31-32.1. In addition, we utilized the 716T/G polymorphism to demonstrate biallelic expression of the adenosine A1 receptor gene in adult human brain.

Adult↗
PubMed1995

Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.

We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees.

Alleles↗
PubMed1995

Lack of genetically determined structural variants of the human serotonin-1E (5-HT1E) receptor protein points to its evolutionary conservation.

Using single strand conformational analysis, we screened the complete coding sequence of the serotonin-1E (5-HT1E) receptor gene for the presence of DNA sequence variation in a sample of 157 unrelated individuals. We detected only a silent C-->T transition at the third position of codon 177. The lack of significant mutations leading to structural variants of the human 5-HT1E receptor protein points to a high evolutionary conservation of this receptor protein.

Base Sequence↗
PubMed1995

A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.

Epilepsy affects at least 2% of the population at some time in their lives. The epilepsies are a heterogeneous group of disorders, many with an inherited component. Although specific genes have been identified in a few rare diseases causing seizures as part of a more diffuse brain disorder, the molecular pathology of the common idiopathic epilepsies is still unknown. Linkage has been reported for some generalised epilepsy syndromes, but only very recently for familial partial epilepsy syndromes. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a partial epilepsy causing frequent, violent, brief seizures at night, usually beginning in childhood. The gene for ADNFLE maps to chromosome 20q13.2-q13.3 in one large Australian kindred. The neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) maps to the same region of 20q (ref. 12) and the gene is expressed in all layers of the frontal cortex. We screened affected family members for mutations within CHRNA4 and found a missense mutation that replaces serine with phenylalanine at codon 248, a strongly conserved amino acid residue in the second transmembrane domain. The mutation is present in all 21 available affected family members and in four obligate carriers, but not in 333 healthy control subjects.

Amino Acid Sequence↗
PubMed1995

Clinical evidence for genomic imprinting in bipolar I disorder.

The phenotypic indicators of the genomic imprinting model were applied to clinical psychopathology data on 100 bipolar (BP) I probands and their families. The paternal transmission was associated with a significantly younger age of onset of the BP illness in probands and a higher rate of affective disorders in first- and second-degree relatives. The effect of the sex of the transmitting parent on age of onset in probands decreased but remained significant when controlling for the effect of the probands' age at investigation. Probands' sex had no significant influence on their age of onset. The severity of the BP illness in probands in terms of number of illness episodes and annual frequency was not influenced by the sex of the transmitting parent.

Adolescent↗
PubMed1995

An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia.

Since abnormalities of brain development play a role in the aetiology of schizophrenia, growth factors, known to play a role in neurodevelopment, such as neurotrophin-3 (NT-3), are therefore candidate genes for this disorder. The A3/147 bp allele of a dinucleotide repeat polymorphism in the promoter region of the NT-3 gene has been reported as occurring more frequently in a sample of Japanese schizophrenics compared to controls. We have determined the frequency of alleles of this polymorphism in 175 Caucasian schizophrenic patients and 147 control subjects. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and, in a test of allalleles, the patients and controls did not differ significantly in allele frequencies. However, the male schizophrenics were more likely than male controls to have the A3/147 bp allele (P = 0.029).

Alleles↗
PubMed1994

Identification of genetic variation in the human serotonin 1D beta receptor gene.

Disturbances of serotonergic pathways have been implicated in a wide variety of neuropsychiatric disorders such as depression, anxiety, migraine, and substance abuse. Genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and/or of pharmacogenetic relevance. Genomic samples from 46 unrelated healthy subjects were investigated by single-strand conformation analysis (SSCA) to screen for genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as 5' untranslated regions of the 5-HT1D beta gene. Four nucleotide sequence variants were found: a coding mutation in nucleotide position 371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the receptor protein and three mutations in the 5' flanking region. For all mutations specific PCR-based assays were developed which allow rapid genotyping in populations and families. To our knowledge, the Phe-124-Cys substitution is the first natural occurring molecular variant which has been identified for the 5-HT1D beta receptor so far.

Alleles↗