Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We collected two clinically matched samples of patients, one sample affected by migraine with aura the other by migraine without aura, to investigate the genetic determination of these conditions. A maternal and X-linked transmission for both these diseases was considered unlikely after pedigree analysis. Classical segregation analysis indicated a likely autosomal recessive kind of transmission for both. Reduced penetrance and the h2 values, however, imply the presence of additional genetic and/or environmental factors controlling the phenotypic expression of migraine.
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PMID:Testing models for genetic determination in migraine. 831 47

We analyzed 31 families selected for an apparently autosomal-dominant mode of inheritance of migraine with aura (MA) in the nuclear family. The nuclear families were expanded with first- and second-degree relatives. All interviews were made by physicians experienced in headache diagnoses. The criteria of the International Headache Society were used. The population relative risk among children in nuclear families was similar to the estimated population relative risk of MA assuming an autosomal-dominant mode of inheritance. The population relative risk tended to decrease among first-degree relatives outside nuclear families and further among second-degree relatives. Both first- and second-degree relatives outside the nuclear families had a statistically significant lower risk of MA than expected. Thus, autosomal-dominant inheritance with or without reduced penetrance was unlikely. Autosomal-recessive inheritance was unlikely because of the unequal sex distribution. Other modes of inheritance were considered as well. Mitochondrial and X-linked inheritance were excluded because of paternal transmission. The female preponderance was too low to explain sex-influenced inheritance. We conclude that MA most likely has a multifactorial inheritance even in high-risk families with MA.
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PMID:Analysis of 31 families with an apparently autosomal-dominant transmission of migraine with aura in the nuclear family. 925 75

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.
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PMID:Evidence for an X-linked genetic component in familial typical migraine. 946 4

Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of urea synthesis. Among females who carry a mutant OTC allele, there is a wide range of phenotypic variability, ranging from apparent normality to a severe onset and the resulting profound neurologic impairment observed in hemizygous males. This study was designed to define the phenotypic variability of OTC deficiency in ostensibly healthy carrier females and to compare them to noncarrier females from their own and other families. One hundred seventy-five women from 89 families participated in this study. Each completed a mailed questionnaire, allopurinol testing, and fasting plasma amino acid determinations. OTC carrier status was determined by pedigree analysis, allopurinol test results, and/or DNA mutation analysis. Overall, 79 women were identified as carriers of a mutant OTC allele (60 proband mothers, 19 relatives), and 96 women (32 proband mothers, 64 female relatives) were determined to be noncarriers. Comparison of biochemical phenotypes indicated that carriers and noncarriers do not differ in daily urinary creatinine excretion, but that carriers excrete significantly less urea nitrogen and total nitrogen, reflecting their significantly lower historically reported daily protein intake. Carriers had significantly higher levels of fasting plasma glutamine and alanine, and significantly lower levels of citrulline and arginine compared with noncarriers. Carriers and noncarriers reported similar demographic characteristics, anthropometric measurements, level of education, and medical and pregnancy histories. There was no indication of increased incidence of migraine headaches among carriers. Thus, we found no evidence that asymptomatic adult female OTC heterozygotes are at increased risk for previously unidentified health problems apart from an unknown risk for hyperammonemic encephalopathy as occurred in 3 of the carriers in this study. Because these episodes appear to be related to physiologic stress (fracture, parturition), it would seem medically prudent for carriers to be aware of this risk.
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PMID:The phenotype of ostensibly healthy women who are carriers for ornithine transcarbamylase deficiency. 985 2

In a previous study we found evidence for an X-linked genetic component for familial typical migraine in two large Australian white pedigrees, designated MF7 and MF14. Significant excess allele sharing was indicated by nonparametric linkage (NPL) analysis using GENEHUNTER (P=0.031 and P=0.012, respectively), with a combined analysis of the two pedigrees showing further increased evidence for linkage, producing a maximum NPL score of 2.87 (P=0.011 ) at DXS 1123 on Xq27. The present study was aimed at refining the localization of the migraine X-chromosomal component by typing additional markers, performing haplotype analysis and applying a more powerful technique in the analysis of linkage data from these two pedigrees. Results from the haplotype analyses, coupled with linkage analyses that produced a peak GENEHUNTER-PLUS LOD* score of 2.388 (P=0.0005), provide compelling evidence for the presence of a migraine susceptibility locus on chromosome Xq24-28.
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PMID:Familial typical migraine: significant linkage and localization of a gene to Xq24-28. 1098 29

The major interest in vertebral artery (VA) hypoplasia comes from its possible connection to migraines with aura as well as from the fact that it is one of the risk factors for a stroke. Therefore, the aim of this preliminary study was to investigate the mode of inheritance of VA hypoplasia. Initially, color Doppler of VA was performed in 64 first- and second-degree relatives of 33 probands, and the presence of VA hypoplasia was confirmed according to the already established criteria. Since a higher prevalence of VA hypoplasia (15.6%) in probands'relatives in comparison with 2.34% in the general population of Croatia was indicative of a strong familial predisposition for this condition, an analysis of family data by means of Pearson's chi-square statistics has been performed. In this analysis, the observed sex-specific frequencies of 36 parent-offspring pairs composed only of affected parent and his/her (affected or non-affected) offspring are compared to the frequencies as expected under eight proposed models. For both--autosomal and X-linked monogenetic inheritance--four hypotheses have been chosen, assuming that the individuals having the affected allele (in combination with a healthy one) have 100%, 50%, 40% and 0% chances of developing VA hypoplasia. Out of eight tested models only two--completely dominant and completely recessive X-linked models--were rejected. But, from the six non-rejected models, goodness-of-fit statistics showed that the hypothesis of X-linked inheritance of VA hypoplasia with the "healthy" allele being stronger (60% effect on phenotype)--almost perfectly fit the data (chi2 = 2.0023; df = 7; p = 0.9597). Further research encompassing a more enlarged family sample is needed to confirm the present findings.
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PMID:Vertebral artery hypoplasia--sex-specific frequencies in 36 parent-offspring pairs. 1181 Dec 80

Migraine is a common complex disorder, currently classified into two main subtypes, migraine with aura (MA) and migraine without aura (MO). The strong preponderance of females to males suggests an X-linked genetic component. Recent studies have identified an X chromosomal susceptibility region (Xq24-q28) in two typical migraine pedigrees. This region harbours a potential candidate gene for the disorder, the serotonin receptor 2C (5-HT(2C)) gene. This study involved a linkage and association approach to investigate two single nucleotide variants in the 5-HT(2C) gene. In addition, exonic coding regions of the 5-HT(2C) gene were also sequenced for mutations in X-linked migraine pedigrees. Results of this study did not detect any linkage or association, and no disease causing mutations were identified. Hence, results for this study do not support a significant role of the 5-HT(2C) gene in migraine predisposition.
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PMID:An investigation of the 5-HT2C receptor gene as a migraine candidate gene. 1255 41

Neuronal voltage-gated calcium channels (VGCCs) are critical to numerous cellular functions including synaptogenesis and neurotransmitter release. Mutations in individual subunits of VGCCs are known to result in a wide array of neurological disorders including episodic ataxia, epilepsy, and migraines. The characterization of these disorders has focused on channel function within the brain. However, a defect in the retina-specific alpha1F subunit of an L-type VGCC results is a loss of visual sensitivity or the incomplete form of X-linked congenital stationary night blindness (CSNB2). Based on the electroretinographic phenotype of these patients this channel type is localized to the axon terminal of photoreceptor cells and results in a loss of signal transmission from photoreceptors to bipolar cells. A mouse with a deletion of the beta2 subunit of VGCCs in the central nervous system was recently shown to have a similar phenotype as CSNB2 patients. The identification of the role of VGCCs in this disorder highlights the potential association of other VGCC mutations with retinal disorders. The study of the role of these channels in normal retinal function may also be elucidated by the characterization of retinal structure and visual function in the numerous knockout, transgenic, and naturally occurring mouse mutants currently available.
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PMID:Using mutant mice to study the role of voltage-gated calcium channels in the retina. 1259 37

Migraine is a common complex disorder characterized by severe recurrent headache and usually accompanied by nausea and vomiting. Previous studies in our laboratory have utilized three large multigenerational Australian pedigrees affected with migraine to indicate that the disease is genetically heterogeneous, with linkage results implicating genomic susceptibility regions on both chromosomes 19p and Xq. The present study explores the possibility of a correlation between genetic and clinical heterogeneity in these affected pedigrees. Specifically, the clinical characteristics of migraine including subtype, age of onset, frequency, duration, and disease symptoms were compared between the migraine pedigrees, and gender differences were also assessed. Our exploratory analyses revealed no significant differences in any of the clinical characteristics tested between the chromosome 19-linked family and the two X-linked families. Also, we did not detect any differences in male vs. female clinical features for these pedigrees. In conclusion, migraine is considered to be a clinically and genetically heterogeneous disorder; however, our study provided no conclusive evidence that variation in genomic susceptibility region is related to heterogeneity at the clinical level in these migraine-affected pedigrees.
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PMID:An analysis of clinical characteristics in genetically linked migraine-affected pedigrees. 1451 Sep 27

Voltage-gated calcium channels are key sources of calcium entry into the cytosol. Mutations in calcium channels have been implicated in numerous disorders such as migraine, incomplete congenital X-linked stationary night blindness, epilepsy, and ataxia, and they are important therapeutic targets for the treatment of pain, stroke, hypertension, and epilepsy. Calcium channel antagonists can be broadly classified into three groups. 1) Inorganic ions typically nonselectively block the pore of most calcium channel subtypes, and in some cases, alter gating kinetics. 2) Peptides isolated from arachnids, cone snails, and snakes frequently selectively antagonize individual calcium channel subtypes by direct occlusion of the pore or altering gating kinetics. 3) Small organic molecules of various structure-activity-relationship (SAR) classes can mediate both selective and nonselective effects on individual calcium channel subtypes, and occlude the pore or reduce channel availability. Here, we provide an overview of classes of inhibitors of non-L-type calcium channels.
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PMID:Molecular pharmacology of non-L-type calcium channels. 1597 66


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