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Biomedical subjects

R Norio

Publications and source records attributed to R Norio.

At least 37 records · Page 2Linked to original sources
PubMed1993

Localization of the EPM1 gene for progressive myoclonus epilepsy on chromosome 21: linkage disequilibrium allows high resolution mapping.

The gene for Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) has previously been mapped by linkage to markers on chromosome 21q22.3. By analyzing crossover events in multiplex disease families with newly detected markers from the region we were able to narrow the localization of EPM1 to an interval of approximately 7 cM, between loci D21S212 and CD18. To further refine the localization of the EPM1 gene we applied linkage disequilibrium mapping in 38 Finnish families, consisting of 12 with multiple affected children and 26 with a single affected child. Based on existing knowledge about the structure and history of the isolated Finnish population, we estimated genetic distances based on strong linkage disequilibrium to several marker loci and found that EPM1 resides within 0.3 cM or less of loci PFKL, D21S25 and D21S154. As this genetic distance translates into a likely physical distance of 300 kb or less, these data provide a basis for highly focused attempts to clone EPM1.

Alleles↗
PubMed1993

Attitudes towards prenatal diagnosis and selective abortion among patients with retinitis pigmentosa or choroideremia as well as among their relatives.

Genetic counselling endeavours to be nondirective. However, the availability of prenatal diagnosis may direct clients towards accepting and using these methods. It is time to investigate the attitudes of clients in order to monitor the psychological and social effects of new genetic techniques. As prenatal diagnosis was possible for choroideremia (C), but not for retinitis pigmentosa (RP) in 1988-89, we used a questionnaire to compare the attitudes of C and RP patients, their relatives and C carriers to prenatal diagnosis. The response rate was low (35%) and no significant differences between RP and C groups came to light. However, C carriers accepted prenatal diagnosis and also selective abortion more easily, but, on the other hand, they showed more uncertainty than did the other groups. This indicates that the availability of prenatal diagnosis may confuse those concerned. In general, about 60% of all the respondents had a positive attitude to the prenatal diagnosis of RP or choroideremia, though only about 30% would use if for abortion. Over 80% of all the respondents wanted to know the opinion of the genetic counsellor.

Abortion, Therapeutic↗
PubMed1993

Intimal thickening of the coronary arteries in infants in relation to family history of coronary artery disease.

BACKGROUND: Intimal thickenings of the coronary arteries of newborn children are composed mainly of smooth muscle cell proliferations. To investigate whether thickening of the intima in infants is associated with a family history of coronary artery disease (CAD), we studied the relation of coronary death of grandparents to intimal thickening of 136 infants. METHODS AND RESULTS: The length of internal elastic lamina of the artery and the areas of arterial layers in cross section were measured, and the arteries were transformed to idealized round circles. Intimal thickening was assessed as the degree of luminal narrowing (ratio of intimal area to the area on the luminal side of the arterial media). Among 136 infants, luminal narrowing varied between 0% and 58%. CAD deaths accounted for 108 of the total 281 deaths among the grandparents of the infants. Family history of CAD (defined as at least one CAD death among the four grandparents) was positive for 77 infants. Family history of CAD was significantly more common in the infants with luminal narrowing of both the left and right coronary arteries compared with the infants with no narrowing in at least one artery (odds ratio adjusted for sex, infection status, and age of infant, 5.69; 95% confidence interval, 1.46-22.2). After adjustment for sex and age, infants with both a positive family history and presence of infection had an increased degree of luminal narrowing compared with infants with a negative family history and no infection. CONCLUSIONS: The association of coronary artery intimal thickening in infancy with family history of CAD suggests that intimal thickening is a morphological manifestation of predisposition to CAD.

Aged↗
PubMed1992

Huntington disease in Finland: a molecular and genealogical study.

Huntington disease (HD) is found at exceptionally low frequency in the Finnish population. In this population, linkage disequilibrium was earlier established with markers from the D4S10 and D4S43 loci. We now report a continuation to the restriction fragment length polymorphism haplotype analysis, in combination with a genealogical study of all the Finnish HD families. When the HD pedigrees were systematically traced to the 18th century, only one consanguinity was found, and a high percentage (28%) of the families had foreign ancestors. The majority of the Finnish ancestors were localized to border regions or trade centers of the country following the old postal routes. The observed high risk haplotypes formed with markers from the D4S10 and D4S43 loci were evenly distributed among the HD families in different geographical locations. Consequently, the HD gene(s) has most probably arrived in Finland on several occasions via foreign immigrants during the last few centuries.

Chromosomes, Human, Pair 4↗
PubMed1992

Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases.

The progressive myoclonus epilepsies (PME) are a heterogeneous group of rare genetic disorders. Unverricht-Lundborg disease and Lafora's disease are two major classic forms of PME. We recently assigned the gene for Unverricht-Lundborg disease (EPM1) to human chromosome 21 band q22.3. We have now refined the localization of EPM1 by linkage analysis between the disease phenotype and nine DNA markers in 13 Finnish families. Loci MX1 and CD18 flank the EPM1 interval, which spans a distance of about 3.5 megabases. In this 20-centimorgan interval, no recombinations were detected between EPM1 and marker loci BCEI, D21S19, D21S42, D21S113, D21S154, and PFKL. Within this interval a maximum multipoint lod score of 11.04 was reached at loci D21S154-PFKL. In two Swedish families with Unverricht-Lundborg disease no recombinations were detected. In three Italian families with Lafora's disease the linkage results suggested that EPM1 is not the locus for Lafora's disease.

Chromosome Mapping↗
PubMed1991

Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22.

Progressive myoclonus epilepsy of Univerricht-Lundborg type is a clinically defined entity among the progressive myoclonus epilepsies. It is an autosomal recessive disorder. The underlying biochemical defect is unknown. We used linkage analysis to localize the gene in 12 families with the aid of polymorphic DNA markers. Close linkage was detected with three markers on distal chromosome 21. The loci BCEI and D21S154 gave the highest positive logarithm-of-odds (lod) scores of 5.49 and 4.25, respectively, at zero recombination. The third locus, D21S112, gave a lod score of 6.91 at a recombination fraction of 0.034. There was no evidence of heterogeneity. Multipoint lod scores calculated against a fixed map of the three marker loci gave a maximum four-point lod score of 10.08 at a location of the disease gene at 6.0 centimorgans distal to locus BCEI and 0.8 centimorgan proximal to locus D21S154. As markers BCEI and D21S154 have previously been localized to 21q22.3 by physical methods, our findings place the EMP1 gene locus (for progressive myoclonus epilepsy of the Unverricht-Lundborg type) in chromosome 21 band q22.3. This finding provides an opportunity to test several other epilepsy phenotypes, particularly the so-called Ramsay Hunt syndrome, for linkage to the same locus. It also is a starting point toward isolating and characterizing the gene and its protein product.

Chromosome Mapping↗
PubMed1991

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal. To investigate other deaminating systems besides MAO-A and MAO-B that might produce these metabolites of dopamine and 5-HT, we examined plasma amine oxidase (AO) activity in these two patients and two additional patients with the same X-chromosomal deletion. Normal plasma AO activity was found in all four Norrie disease-deletion patients, in four patients with classic Norrie disease without a chromosomal deletion, and in family members of patients from both groups. Marked plasma amine metabolite abnormalities and essentially absent platelet MAO-B activity were found in all four Norrie disease-deletion patients, but in none of the other subjects in the two comparison groups. These results indicate that plasma AO is encoded by gene(s) independent of those for MAO-A and MAO-B, and raise the possibility that plasma AO, and perhaps the closely related tissue AO, benzylamine oxidase, as well as other atypical AOs or MAOs encoded independently from MAO-A and MAO-B may contribute to the oxidative deamination of dopamine and 5-HT in humans.

Adolescent↗
PubMed1991

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome).

We describe 14 patients, from 11 families, who have a progressive encephalopathy with early onset. The clinical signs of the disease are severe hypotonia, convulsions with hypsarrhythmia, profound mental retardation, hyperreflexia, transient or persistent edema, and optic atrophy. These findings and the characteristic dysmorphic features allow recognition of these patients, although no basic metabolic defect has been found. Microcephaly and atrophy of the brain develop, especially in the cerebellar and brain stem areas. An autosomal recessive mode of inheritance is likely.

Brain↗
PubMed1991

Abnormal protein in the cerebrospinal fluid of patients with a submicroscopic X-chromosomal deletion associated with Norrie disease: preliminary report.

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and, in many cases, mental retardation. Some Norrie disease cases have been shown to be associated with a submicroscopic deletion in chromosomal region Xp11.3. Cerebrospinal fluid (CSF) was collected from four male patients with an X-chromosomal deletion associated with Norrie disease. CSF proteins were resolved using two-dimensional gel electrophoresis and then analyzed by computer using the Elsie V program. Our analysis revealed a protein that appears to be altered in patients with Norrie disease deletion.

Blindness↗
PubMed1990

Cystic fibrosis mutation delta F508 in Finland: other mutations predominate.

The frequency of mutation delta F508 was determined in all 20 Finnish cystic fibrosis (CF) families with living affected children (19 with pancreatic insufficiency). delta F508 was detected in 18 out of 40 CF chromosomes (45%). At least two different mutations associated with pancreatic insufficiently have occurred in a rare haplotype defined by XV2c, CS.7, KM19 alleles 1 2 2. Geographical clustering of delta F508 and other mutations suggested that a founder effect and genetic drift have influenced the frequency of mutations causing CF in Finland.

Child↗
PubMed1990

Intimal thickening in the coronary arteries of infants and children as an indicator of risk factors for coronary heart disease.

Narrowings of the coronary arteries were measured in 94 infants aged less than 1 year who died in hospital and 102 1- to 16-year-old children who died accidentally. The arteries were transformed mathematically to circles. The degree of narrowing caused by intimal thickening was determined as the ratio of intimal area to the original luminal area. This ratio was further transformed to percentage. The degree of narrowing varied between 0 and 58% (mean 20%). The mean degree of narrowing in the left coronary artery during the first year of life was 17% and, between 12 and 15 years, 34%. Narrowing was greater in males (P = 0.02), when all the 333 coronary samples were included in the analysis. The birthplaces of the subjects' grandparents were traced from population registers and it was found that narrowing in the left coronary artery of infants was greater in those descended from grandparents from eastern Finland, an area of high mortality from coronary heart disease (CHD). Intimal thickening in infants and children seems to be a morphological manifestation of hereditary predisposition to CHD.

Adolescent↗
PubMed1990

Marked amine and amine metabolite changes in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Urinary and plasma amines and amine metabolites were quantified in two individuals with Norrie disease resulting from a deletion in chromosomal region Xp11.3, recently reported to be associated with absence of the gene encoding monoamine oxidase (MAO)-A and nondetectable MAO-A activity in fibroblasts and MAO-B activity in platelets. Marked (four-to 100-fold) elevations in levels of urinary phenylethylamine, o-tyramine, and m-tyramine (which are preferential substrates for MAO-B) and marked reductions (90%) in levels of 3-methoxy-4-hydroxyphenylglycol (a deaminated metabolite of norepinephrine, a preferential substrate for MAO-A) in urine and plasma confirmed the presence of a systemic, functionally significant reduction in the activities of both MAO isozymes. The magnitude of these changes, which are equivalent to those found in subjects taking MAO-inhibiting antidepressants, suggests that early initiation of dietary and drug restrictions may be clinically important in these and other patients with X-chromosomal mutations involving MAO. These findings further support the proposition that the MAOA and MAOB genes are located in close proximity on the X chromosome. Negligible changes in the metabolites of dopamine and serotonin raise the possibility that other metabolic pathways are of importance for their production, that dietary or intestinal bacterial sources contribute substantially to the presence of these amine metabolites in urine, or both.

Adolescent↗
PubMed1989

RAPADILINO syndrome with radial and patellar aplasia/hypoplasia as main manifestations.

A new malformation syndrome is described in a pair of sibs and 3 sporadic patients. The characteristic manifestations are radial aplasia or hypoplasia, absence of thumbs, absent or hypoplastic patellae, dislocations of joints, unusual face, cleft or highly arched palate, diarrhea in infancy, small stature, and normal intelligence. Recessive inheritance seems the most plausible cause. The acronym RAPADILINO syndrome is proposed.

Adolescent↗
PubMed1989

Cystic fibrosis in Finland: a molecular and genealogical study.

The incidence of cystic fibrosis (CF) in Finland is one tenth that in other Caucasian populations. To study the genetics of CF in Finland, we used a combined molecular and genealogical approach. Out of the 20 Finnish families with a living CF patient, 19 were typed for eight closely linked restriction fragment length polymorphisms (RFLP) at the MET, D7S8, and D7S23 loci. The birthplaces of the parents and grandparents were traced using population registries. Allele and haplotype frequencies in Finland are similar to those of other European and North American populations, but are modified by sampling: two regional CF gene clusters, evidently the results of a founder effect, were identified. Generally, the gene was evenly distributed over the population, carrier frequency being estimated at approximately 1.3%. We conclude that CF in Finland is caused by the common Caucasian mutation(s), and that the low frequency of the gene can be explained by a negative sampling effect and genetic drift.

Adult↗
PubMed1989

Monoamine oxidase deficiency in males with an X chromosome deletion.

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

Adolescent↗