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Biomedical subjects

P Propping

Publications and source records attributed to P Propping.

At least 109 records · Page 6Linked to original sources
PubMed1998

Genetic counseling in a patient with XXY/XXXY/XY mosaic Klinefelter's syndrome: estimate of sex chromosome aberrations in sperm before intracytoplasmic sperm injection.

OBJECTIVE: To report the sex chromosome aberrations in the sperm of a patient with mosaic Klinefelter's syndrome before ICSI. DESIGN: Case report. SETTING: Institute of Human Genetics, University Hospital PATIENT(S): A patient with an XXY/XXXY/XY mosaic Klinefelter's syndrome and extreme oligozoospermia. INTERVENTION(S): Skin biopsy, buccal smear, hair root sampling, and semen sampling. MAIN OUTCOME MEASURE(S): The karyotypes of three additional somatic cell systems and the ratio of sex chromosome aberrations in sperm. RESULT(S): After two-color fluorescence in situ hybridization of 202 interphase sperm nuclei, both the proportion of hyperhaploid 24, XY and 25, XXY sperm (5.0% and 0.5%, respectively) and of hyperhaploid 24, XX sperm (2.0%) were elevated. In contrast with peripheral lymphocytes, 93.9% of which showed sex chromosome aberrations, in the present patient only 7.5% of sperm proved to be hyperhaploid with an extra sex chromosome. CONCLUSION(S): The determination of sex chromosome aberrations in the sperm of a patient with mosaic Klinefelter's syndrome may provide additional information to estimate the transmission risk to his offspring.

Adult↗
PubMed1998

Lack of association between dopamine D4 receptor gene and personality traits.

BACKGROUND: Personality traits have shown considerable heritable components. Association between alleles of a polymorphism in the third exon of the dopamine D4 receptor gene (DRD4) and the personality trait Novelty Seeking has been reported. Recently, in a sample of Swedish non-psychiatric subjects we could not detect any significant relationships between the same polymorphism and Novelty Seeking related scales in the Karolinska Scales of Personality (KSP). However, there was a tendency in the direction of the proposed association. There were also tentative associations between an exon I 13 bp deletion polymorphism and the personality traits Socialization and Guilt. METHODS: We investigated a new Swedish population-based sample (N = 167) investigated with the KSP for three DRD4 polymorphisms. RESULTS: Neither of the previous results were replicated. Combining the previous and the present samples did not give rise to any significant association between DRD4 polymorphisms and personality scales. CONCLUSIONS: The dopamine D4 receptor gene is probably not of importance to the different personality dimensions as measured by the Karolinska Scales of Personality.

Adult↗
PubMed1998

Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease.

Several lines of evidence suggest a contribution of adenosinergic neurotransmission to the development of panic disorder. We therefore hypothesized that variation in the A1 and A2a adenosine receptor (AR) genes modifies genetic susceptibility to panic disorder. To test this hypothesis, we screened 38 patients with panic disorder for mutations in the coding sequence of the A1AR and A2aAR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched controls. One silent mutation (716T/G) in the A1AR gene and two silent mutations (432C/T and 1083C/T) in the A2aAR gene were detected. The association sample shows a significant association between the 1083T allele (P=0.01) and 1083T/T genotype (P=0.024) of the A2AR gene and panic disorder. Our findings thus lend further support to the hypothesis that the A2aAR gene, or a locus in linkage disequilibrium with it, confers susceptibility to panic disorder. Replication studies in independent samples with nuclear families applying the transmission disequilibrium test (TDT) are warranted.

DNA Primers↗
PubMed1998

A gene for universal congenital alopecia maps to chromosome 8p21-22.

Complete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development.

Alopecia↗
PubMed1998

Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria.

Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the coincidence of at least one sebaceous skin tumor and one internal malignancy. About half of MTS patients are affected by colorectal cancer. In a subgroup of MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC). The purpose of this study was to examine to what extent germ-line mutations in DNA MMR genes are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients with sebaceous skin tumors and colorectal cancer, and we examined their skin and visceral tumors for microsatellite instability. All the patients exhibited high genomic instability in at least one tumor. The search for germ-line mutations in the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is the first systematic search for germ-line mutations in patients ascertained on the basis of sebaceous skin tumors. Our results indicate that (1) MTS patients exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene; and (2) the subpopulation of MTS patients who are also affected by colorectal cancer, irrespective of family history and age at onset of tumors, may have a likelihood for an underlying DNA MMR defect similar to that for patients with a family history fulfilling the strict clinical criteria for HNPCC.

Adult↗
PubMed1998

Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia.

Complete or partial congenital absence of hair (congenital alopecia) may occur isolated or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal recessive mode of inheritance (MIM 203655). We have previously mapped the gene for autosomal recessive congenital alopecia in a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia) to a 15 cM region on chromosome 8p21-22. Here we report the cloning and characterization of the human homologue of the mouse hairless gene and show that it is located in the critical region on chromosome 8p21-22. Determining the exon-intron structure allowed detailed mutational analysis of DNA samples of patients with universal congenital alopecia. We detected a homozygous missense mutation in the Pakistani family and a homozygous splice donor mutation in a family from Oman. In addition, we show that the human hairless gene undergoes alternative splicing and that at least two isoforms generated by alternative usage of exon 17 are found in human tissues. Interestingly, the isoform containing exon 17 is the predominantly expressed isoform in all tissues but skin, where exclusive expression of the shorter isoform was observed. We speculate that this tissue-specific difference in the proportion of hairless transcripts lacking exon 17 sequences could contribute to the tissue-specific disease phenotype observed in individuals with isolated congenital alopecia.

Adult↗
PubMed1997

Possible association of a silent polymorphism in the neuronal nicotinic acetylcholine receptor subunit alpha4 with common idiopathic generalized epilepsies.

The alpha4 subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA4) has recently been identified as the first gene underlying an idiopathic partial epilepsy syndrome in human, autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE). CHRNA4 is located in the candidate region for benign familial neonatal convulsions and low-voltage EEG on chromosome 20q. In the present study, we examined the possible role of CHRNA4 in common subtypes of idiopathic generalized epilepsy (IGE), comprising childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy (JME), by systematically screening the coding region of the gene for sequence variants. We present here a population-based association study testing the hypothesis that variants of the CHRNA4 gene confer genetic susceptibility to common subtypes of IGE. The missense mutation (Ser248Phe), associated with ADNFLE, and four silent polymorphisms in the CHRNA4 gene were genotyped in 103 IGE patients and 92 controls by polymerase chain reaction and subsequent restriction analysis. Without correction for multiple testing, the frequency of the T-allele of the silent CfoI bp595 polymorphism was increased in the entire group of IGE patients (f(T) = 0.085) compared to that in the controls (f(T) = 0.027). The allelic association was not restricted to any subgroup of IGE with either JME or idiopathic absence epilepsies. This result suggests that variation of the CHRNA4 gene, or so-far-undetected sequence variants near the CHRNA4 locus, confer susceptibility to the common IGE syndromes.

Alleles↗
PubMed1997

Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor.

In the present study we tested the hypothesis that individual response to clozapine treatment and/or the occurrence of side-effects may be influenced by genetic variation in the serotonin 5-HT2C receptor. We investigated the frequency of a common Cys23Ser substitution, which is known to alter the pharmacological properties of the protein, in 152 patients treated with clozapine. Presence of the Ser23 variant was previously reported to predict a good response to clozapine. However, our results did not support an association between genetic variation of the 5-HT2C receptor and response to clozapine. This held true whether the patients were subgrouped for sex and length of treatment. Moreover, we found no consistent association with any of the observed side-effects.

Adult↗
PubMed1997

Neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and panic disorder: an association study.

Anxiety disorders have been reported to be associated with low-voltage EEG (LVEEG). Some cases with LVEEG (approximately 1/3) have been linked to chromosome 20q13.2q13.3. In the same chromosomal region, the gene for the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) has been located. We therefore tested the hypothesis that polymorphisms in the CHRNA4 gene show an allelic association with panic disorder. We examined the allele frequencies of three different CHRNA4 polymorphisms in patients with panic disorder and in healthy controls. No significant differences in the allele frequencies of these three polymorphisms were noted. This study does not support an association between panic disorder and the CHRNA4 gene.

Adult↗
PubMed1997

Human 5-HT5A receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 7q34-q36 using a polymorphism in the 5' untranslated region.

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide range of sensory, motor, and cortical functions by activating multiple 5-HT receptor subtypes. In the present study we performed a systematic mutation scan of the complete coding region of the 5-HT5A receptor to explore its variability in the general population. Investigating 46 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. The detection of a frequent G-->C substitution at position -19 was used for fine scale linkage mapping of the 5-HT5A gene. Employing a polymerase-chain-reaction based assay we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor to genetic markers on chromosome 7q34-q36.

Chromosome Mapping↗
PubMed1997

5-HT2A receptor and bipolar affective disorder: association studies in affected patients.

The aim of this study was to investigate the possible involvement of genetic variation in serotonin receptors in the aetiology of bipolar affective disorder. The 5-HT2A receptor gene was systematically screened for genetic variants by single strand conformation polymorphism (SSCP) methods in subjects with bipolar affective disorder. Four polymorphisms (two structural changes, Thr25Asn and His4 M52Tyr, and two silent polymorphisms, 102-T/C and 516-C/T) which had previously been found in patients with schizophrenia and control subjects were detected. No novel polymorphisms were found in patients with bipolar affective disorder. These polymorphisms were genotyped in a sample of 129 patients and 252 controls of German origin and 176 patients and 182 controls of British origin. No strong associations were found between any of these polymorphisms and bipolar affective disorder. Genetic variation at the 5-HT2A receptor gene does not play a major role in the pathogenesis of the disorder.

Alleles↗
PubMed1997

Mapping of the human adenosine A2a receptor gene: relationship to potential schizophrenia loci on chromosome 22q and exclusion from the CATCH 22 region.

Chromosome 22 contains two potential schizophrenia loci on chromosomal regions 22q11.2 and 22q12-13. In the present study we report results from linkage mapping of the gene coding for the human A2a adenosine receptor (AR), which is one of two receptors mediating central nervous system effects of adenosine. From seven CEPH (Centre d'Etude du Polymorphisme Humain) families, 120 individuals were typed utilizing an intragenic restriction fragment length polymorphism. Significant linkage was found with many markers on chromosome 22. A 10-cM 1000:1 support interval between markers D22S301 and D22S300 is defined on the CHLC (Cooperative Human Linkage Center) framework map of chromosome 22. Localization of the A2aAR gene outside the CATCH 22 syndrome region on 22q11.2 is demonstrated by the observation of heterozygous individuals with defined 2-Mb deletions from this region. Thus, the A2aAR gene is not the schizophrenia susceptibility gene suspected in the CATCH 22 syndrome region on 22q11.2, but remains a candidate for a schizophrenia susceptibility gene on 22q12-13.

Abnormalities, Multiple↗
PubMed1997

Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue.

Evaluation of the causative role of germline mutations in DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) families can be difficult. Whereas nonsense, frameshift or splice-site mutations are presumed to lead to dysfunctional gene products and thus are generally considered to be causative, the evaluation of missense mutations often remains uncertain. We observed a novel germline mutation in the hMLH1 gene (His-->Pro at codon 329) in an HNPCC family. The same missense mutation also occurred as a somatic event in the colonic tumours of two other HNPCC patients who had germline mutations at different sites of the hMLH1 gene. Thus, the H329P mutation present in the germline can be considered as having an aetiological role in this HNPCC family.

Adaptor Proteins, Signal Transducing↗