Significantly earlier age at onset for the HLA-Cw6-positive than for the Cw6-negative psoriatic sibling.
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Age of Onset↗
Biomedical subjects
T Martinsson
Publications and source records attributed to T Martinsson.
Evidence that HLA-Cw6 determines early onset of psoriasis, obtained using sequence-specific primers (PCR-SSP).
Psoriasis vulgaris has previously been shown to associate with certain HLA alleles. HLA-Cw6 is considered to be the primary association, based on calculations of relative risk after serological typing. This association is reportedly more pronounced in early- than in late-onset psoriasis. We performed a PCR-based typing with sequence-specific primers, which has been shown to give a more complete result than serology. Two hundred and one unrelated patients with psoriasis, with a mean age of 40 years, and 77 healthy controls were typed. Two thirds (67%) of the patients were positive for one or two copies of the allele, while the corresponding figure for the control group was 12%. A significant peak for age at onset of 21 or younger was seen for the Cw6 carriers. For patients older than 21 at onset, the frequency of Cw6 was significantly lower; e.g. for patients with an age at onset between 30 and 35 the frequency was comparable to the level of the control group. The high frequency of Cw6 among patients with an age at onset of 21 or younger is in agreement with data of other groups. In comparison with this age-at-onset group the frequency of Cw6 is sharply reduced among patients with an age at onset of 22 years or older, which contrasts with earlier studies. This may reflect differences between population groups but may also be due to the higher sensitivity of the PCR-based HLA-Cw6 typing method. In view of these findings, we suggest that psoriasis is a genetically determined disease, in which the additional presence of HLA-Cw6 is associated with the characteristic of early onset.
Adult↗
Ropivacaine inhibits leukocyte rolling, adhesion and CD11b/CD18 expression.
Ropivacaine, a new local anesthetic, is currently being investigated for the treatment of ulcerative colitis, with promising results so far. The aim of this study was to examine anti-inflammatory properties of ropivacaine with regard to its effects on vascular permeability and inflammatory leukocyte behavior in vivo. The effects on leukocyte rolling, firm adhesion and vascular permeability were examined in the hamster cheek pouch microvasculature via intravital microscopy, and the effects on leukocyte adhesion molecules were examined in vitro by means of flow cytometry. In large venules, leukocyte adhesion induced by topical leukotriene B4 (LTB4) was almost completely inhibited during the combined application of ropivacaine and LTB4. The spontaneous rolling leukocyte flux was reduced by 72%, the rolling leukocyte fraction by 47% and the total leukocyte flux, which reflects blood flow, by 47%. In postcapillary venules, ropivacaine abolished rolling and LTB4-induced firm adhesion of leukocytes. LTB4 challenge also resulted in increased plasma exudation that was almost completely inhibited by ropivacaine. Moreover, ropivacaine inhibited the tumor necrosis factor alpha-induced up-regulation of CD11b/CD18 and L-selectin shedding by human leukocytes in vitro. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated to a significant extent by inhibition of both leukocyte rolling and adhesion.
Amides↗
Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands.
The risk of getting psoriasis dependent on the occurrence of psoriasis in the family has been determined empirically. Altogether 3717 families with one or both parents who had psoriasis have been analysed with regard to the number of children with or without psoriasis. The lifetime risk of getting psoriasis if no parent, one parent or both parents have psoriasis is 0.04, 0.28 and 0.65, respectively. If there is already one affected child in the family, the corresponding risks are 0.24, 0.51 and 0.83, respectively. The risk of getting psoriasis before the age of 32 years is dependent on the age-of-onset of psoriasis in one affected parent.
Adolescent↗
Maternal origin of inv dup(15) chromosomes in infantile autism.
Six male patients with infantile autism and an extra inverted duplicated chromosome 15[inv dup(15)] were reported in a previous study. These patients had four copies of the chromosome region 15pter-q13, or an inv dup(15)(pter-->q13; q13-->pter). In this new study, DNA from the families of four of the patients were analysed using Southern based RFLPs and microsatellite polymorphisms from the region. In all four cases the inv dup(15) chromosome was of maternal origin. Furthermore, the data suggests that it originated in the maternal meiotic process rather than in an early mitosis in the developmental process of the embryo. The extra chromosome contained material from both of the maternally derived 15-chromosomes. Based on the molecular data presented here, a model for the origin of chromosome markers of this type is proposed.
Abnormalities, Multiple↗
No genetic linkage between multiple sclerosis and the interferon alpha/beta locus.
Multiple sclerosis (MS) is probably caused by an interaction of genetic and environmental factors. The genetic component is reflected by a ten-fold higher concordance rate in monozygotic (27%) compared to dizygotic (3%) twin pairs. Treatment with interferon was recently reported to have a favorable effect in patients with relapsing-remitting MS. In the present familial study, we have investigated the possibility of a genetic association between the highly polymorphic Interferon alpha beta locus and the development of MS. Based on our data, we conclude that there is no linkage between the Interferon alpha beta locus and MS.
Adult↗
Report of the sixth international workshop on human chromosome 3 mapping 1995.
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Animals↗
Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas analyzed with short-tandem repeat polymorphisms.
We have analyzed DNA from 46 neuroblastoma tumors of all clinical stages and five ganglioneuroma tumors together with corresponding control DNA for loss of heterozygosity (LOH) on the distal 1p chromosomal region (1p-LOH). The markers used for the analyses were genetically mapped DNA polymorphisms detectable with PCR analysis. In general, there was concordance among aggressive tumor stage, 1p deletion, and N-myc amplification, although exceptions were found. Twelve (26%) of the 46 neuroblastoma tumors displayed 1p-LOH, 11 being stage 4 and 1 stage 2 (which progressed subsequently to stage 4), whereas 10 stage 4 tumors showed no 1p-LOH. Of 12 neuroblastomas shown to have N-myc amplification, 10 had 1p-LOH. In 8 cases it was possible to test for parental origin of the chromosome involved in 1p-LOH. No significant correlation between LOH and paternal or maternal allele was found. Commonly deleted loci in the distal 1p region in the neuroblastoma tumors indicated that the region for a tentative neuroblastoma tumor suppressor gene is defined proximally by marker D1S244 and distally by marker D1S80. One striking feature of three stage 2 neuroblastomas and one of the stage 3 tumors was the presence in the tumor DNA of alleles not present in the constitutional DNA of the patients, i.e., microsatellite instability. The significance of this phenomenon in localized neuroblastoma tumors remains to be clarified. Aggressive neuroblastoma in young children (younger than 2 years of age) seems to be a homogenous disorder consistently showing concomitant 1p-LOH and N-myc amplification. In the majority of unfavorable neuroblastoma in older children, however, neither 1p-LOH nor N-myc amplification could be detected. This indicates that neuroblastoma in older children is a biologically more heterogenous disorder in which genetic alterations other than deletions of chromosome 1p and amplification of N-myc also may contribute to tumorigenesis.
Child↗
[von Hippel-Lindau hereditary tumor syndrome. Mutational analysis may improve prognosis].
The von Hippel-Lindau disease is a familial tumour syndrome characterised by greatly increased risks of developing central nervous haemangioma, renal cell carcinoma, retinal angioma and pheochromocytoma. Carriers have inherited a mutated tumour suppressor gene located at chromosome 3p25-26. The VHL gene has recently been cloned, three exons identified and the DNA sequence determined. A Swedish kindred comprising four generations and 41 individuals was investigated. Three living individuals with clinically verified VHL disease demonstrated a single base deletion of a cytosine residue at position 761 of the VHL gene, corresponding to amino acid 254. Among the remaining family members, two asymptomatic carriers of this VHL mutation were identified and offered a clinical follow-up programme for early detection and treatment of future VHL manifestations.
Adult↗
Age at onset and different types of psoriasis.
The age at onset of psoriasis has been analysed for 11,366 psoriasis patients. The age at onset for siblings of probands has been analysed for 805 probands having one affected sibling and for 179 probands having two affected siblings. The age at onset curve for all probands shows a dominating maximum at about puberty but also indications for two more maxima at about 30 and 50 years of age, respectively. A more relevant picture of the risk of getting psoriasis at different ages is obtained if the onset for old people having psoriasis is investigated. The three maxima come out more clearly in this case, and the puberty maximum is not so dominating. For the families with one proband and two affected siblings there is a statistically significant correlation (P < 0.001) between the age at onset of the proband and of the siblings, and also between the siblings. The correlation coefficient is between 0.30 and 0.45. For the probands with one affected sibling, the ages at onset of the siblings mainly fall in the same range as those of the probands. These data indicate three groups of patients with respect to age at onset. However, the overlap between the different groups is considerable. The data presented are compatible with three, possibly genetically different, variants of psoriasis vulgaris. By studying the occurrence of psoriasis among parents of the probands, the gene frequency can be estimated assuming a recessive mode of inheritance. It then turns out that the gene frequency of the group with the earliest age at onset has a gene frequency of about 0.25, the next earliest, 0.18, and the latest, 0.14.
Adolescent↗
Utilization of dental services in refugees in Sweden 1975-1985.
Prior to 1940 the population of Sweden was one of the most homogeneous in Europe, with only 0.5% foreign born. Fifty years later, in 1990, the proportion of immigrants was around 15%. In order to describe and analyze consumption of dental care in different refugee groups in Sweden, data registered by the Department of Immigration and the National Social Insurance Board, on a random sample of 2489 refugees arriving in Sweden 1975-85, were merged. Information on nationality, date of arrival in Sweden, date of granting of permanent resident status and statistics on consumption of dental care were retrieved. During the period studied a total of 50,521 refugees arrived in Sweden. The average interval between arrival in Sweden and the first dental visit was 4.5 yr (95% < 1: 4.2-4.7). The total treatment time during the first course of treatment was 165.5 min (95% < 1: 148.7-182.3). Consumption of dental care did not decrease with an increased number of treatments. Only 38% of the refugees had visited a dentist at all in Sweden. With increasing number of years in Sweden the number of courses of dental treatment increased, but 41% of the refugees who had visited the dentist in Sweden had done so only once. This study shows a low utilization of dental services among refugees in Sweden in general. Refugees with dental visits in Sweden, in particular, had a high dental consumption.
Adolescent↗
Computerized measurements of the lower third molar related to chronologic age in young adults.
Chronologic age is an utmost important birth record in many industrialized Western countries. When the date of birth is unknown, there is a demand for establishing the chronologic age. Dental methods for age estimations are considered more reliable than most other methods by the majority of researchers and are among the most commonly used means to determine age. Traditionally, these methods have most often been based on subjectively estimated, radiographic stages of tooth development. In the present study metric measurements of the length of the forming root have been used and are compared with one standard method. The formed part of the root of the lower third molar as seen in a panoramic radiograph was digitized. Data were directly stored in a computer for subsequent statistical analysis. The technique of collecting data with the aid of a computer had some statistical advantages. The precision of age estimations was, however, slightly inferior to the standard method.
Adolescent↗
Progress in a genome scan for linkage in schizophrenia in a large Swedish kindred.
Genetic linkage studies of a kindred from Sweden segregating for schizophrenia have been performed using a genetic model (autosomal dominant, f = 0.72, q = 0.02, phenocopies = 0.001) as described in Kennedy et al., 1988. Analyses of the restriction fragment length polymorphism (RFLP), allele-specific oligonucleotides (ASO), and short tandem repeat (STR also called microsatellite) data for 180 polymorphisms (individual probe-enzyme, ASO, or STR systems) at 155 loci have been completed using the MLINK and LIPED programs. Linkage to schizophrenia was excluded, under the given model, at 47 loci; indeterminate lod scores occurred at 108 loci. The total exclusion region across 20 chromosomes is estimated at 330 cM; 211 cM excluded by pairwise analyses and 119 cM previously excluded by multipoint analyses (Kennedy et al., 1989: Schizophr Bull 15:383-391; Moises et al. 1991: Genet Epidemiol 2:99-110; Hallmayer et al., 1992: Arch Gen Psychiatry 49:216-219).
Alleles↗
HLA and prognosis in multiple sclerosis.
The patients of a multiple sclerosis (MS) incidence cohort with 25 years of longitudinal follow-up were typed for HLA-DR and DQ. This type of cohort provides reliable data for gene frequencies and prognostic studies. The influence of sampling bias, mainly due to mortality during the long follow-up, was accounted for. A positive association between MS and DR15,DQ6 was confirmed, but this haplotype did not influence prognosis. There was no difference in haplotype frequency between relapsing-remitting and primary chronic progressive MS. DR17,DQ2 was significantly over-represented in the quartile with the most malignant course. The haplotype DR1,DQ5, which was found rather less frequently in MS patients, also tended to be associated with a poorer prognosis.
Aged↗
A population genetic study of psoriasis.
We present epidemiological data for 5197 families with psoriasis. Errors in reporting have been analysed. Analysis of the data provides indications of random mating with respect to whether the partner has the skin disease or not. Data on psoriasis among parents, siblings and children are provided, and particular attention has been paid to the age at onset of psoriasis. Psoriasis was present in the parents of about 36% of the probands. In families in which one or both parents have psoriasis, the occurrence of the disease among the siblings does not provide any information which differentiates between a dominant and recessive mode of inheritance, but is compatible with both. In families in which neither parent had psoriasis, provided there was a proband with psoriasis, the probability of the siblings suffering from psoriasis was close to 0.25, indicating a recessive mode of inheritance. The distribution of psoriasis among the parents of all probands, and among the children of probands, was also compatible with this mode of inheritance. The prevalence of psoriasis in the elderly was estimated to be about 5%, and the gene frequency in the whole population 25%. These findings show that, with regard to first-degree relatives, the inheritance of psoriasis can fit an autosomal recessive model. The concept of a recessive mode of inheritance may be used as a basis for genetic counselling.
Adult↗
Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family.
We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post-mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage.
Adolescent↗
Dilated cardiomyopathy and the dystrophin gene: an illustrated review.
Cardiomyopathy is often found in patients with Duchenne and Becker muscular dystrophy, which are X linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects present in many different ways and cases of mild Becker muscular dystrophy have been described in which cardiomyopathy was severe. Female carriers of Duchenne muscular dystrophy can develop symptomatic skeletal myopathy alone or combined with dilated cardiomyopathy. They can also develop dilated cardiomyopathy alone. X linked dilated cardiomyopathy has been found in association with dystrophin defects. The relation between the molecular defects and the cardiac phenotypes has not yet been established. New mutations in the dystrophin gene are common and such mutations cause one third of the cases with Duchenne and Becker muscular dystrophy. This means that sporadic cases of cardiomyopathy caused by dystrophin defects are likely. This paper reports such a case in a boy of 14 who died of dilated cardiomyopathy. Before the cardiac investigation, which was performed one month before he died, he had not complained of muscular weakness. He had minor signs of limb girdle myopathy and slightly increased concentrations of serum creatine kinase. He was found to have an unusual deletion in the dystrophin gene.
Adolescent↗
Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406.
Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as an autosomal recessive trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to localize the gene (CDG1) with linkage techniques. We analyzed individuals from 25 CDG1 pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta max = 0.00) for several markers in this region. In order to further localize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406 indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us. The positions of cytogenetically localized flanking markers suggest that the location of the CDG1 gene is in chromosome region 16p13.3-p13.12.
Alleles↗