RESUMEN
The prevalence of the familial defective apolipoprotein B-100 (FDB) Arg3500Gln mutation in 525 unrelated hypercholesterolaemic Polish subjects was evaluated. DNA samples were screened for FDB mutation using SSCP method. Presence of mutation was confirmed using a mismatch MspI PCR strategy. Plasma lipid levels and clinical characteristics of 13 patients identified as carriers of the mutation and of their 23 affected relatives were analysed and compared with non-affected ones. In the affected individuals a variable expression of lipid concentrations and of atherosclerosis symptoms were observed. The prevalence of FDB Arg3500Gln mutation in hypercholesterolaemic Polish subjects (3.7%) seems to be similar to the frequency reported in other Caucasian hypercholesterolaemic populations. The estimated prevalence of the mutation in general Polish population is relatively high being 1/250. The same haplotype at the apoB locus in the carriers of this mutation in Poland as in other populations from Western Europe suggests its common origin. In one hypercholesterolaemic subject a non-hitherto described mutation was identified. It consisted in C-->T transition in apoB codon 3492 leading to threonine to isoleucine substitution in 3492 position of apoB gene (Thr3492Ile).
Asunto(s)
Apolipoproteínas B/genética , Hipercolesterolemia/genética , Adulto , Anciano , Anciano de 80 o más Años , Apolipoproteína B-100 , Secuencia de Bases , ADN/química , ADN/genética , Análisis Mutacional de ADN , Femenino , Haplotipos , Humanos , Hipercolesterolemia/epidemiología , Masculino , Persona de Mediana Edad , Mutación , Mutación Missense , Polonia/epidemiología , Polimorfismo Conformacional Retorcido-Simple , PrevalenciaRESUMEN
Arylsulfatase A (ASA) pseudodeficiency (PD) allele was searched for in 22 patients originating from Poland and suffering from different types of metachromatic leukodystrophy (MLD). Four of them carried the PD allele in a heterozygous state. The prevalence of the PD allele among investigated MLD patients was revealed to be 9%, while the frequency of the PD allele in healthy controls was estimated at 6-7%. One of the examined MLD patients was additionally a carrier of an isolated mutation leading to the loss of the N-glycosylation site. The question arises whether and how MLD mutations create a convenient milieu for PD mutations to occur (or inversely).
Asunto(s)
Alelos , Cerebrósido Sulfatasa/deficiencia , Cerebrósido Sulfatasa/genética , Leucodistrofia Metacromática/epidemiología , Leucodistrofia Metacromática/genética , Femenino , Humanos , Polonia/epidemiología , PrevalenciaRESUMEN
In 64 individuals with dementia (26 Alzheimer type, 34 of vascular origin and 4 other types of dementia) apolipoprotein E genotype was identified. Frequency of epsilon4 allele was 36.5% in Alzheimer patients and 32.4% in vascular dementia ones. In a group of 39 nondemented individuals of the same age the epsilon4 frequency was 11.5%. In demented patients, carriers of epsilon4, a tendency to higher plasma levels of atherogenic lipids (total cholesterol and low-density lipoprotein cholesterol) as compared with noncarriers was observed. It is possible that the epsilon4 form may aggravate the course of dementia through a moderate influence on the atherogenic lipoprotein level. The results showed that both Alzheimer disease and vascular dementia shared the same risk factors which is consistent with current opinion about a link existing between these two types of dementia.
Asunto(s)
Apolipoproteínas E/genética , Demencia/sangre , Demencia/genética , Lípidos/sangre , Lipoproteínas/sangre , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Colesterol/sangre , Demencia Vascular/sangre , Demencia Vascular/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
In families with Duchenne/Becker muscular dystrophy, DNA analysis allows direct detection of the sex-linked dystrophy gene mutation. The detection of two alleles (heterozygous) in the region of a deletion in an affected son, excludes the mother having the same deletion. However, it is known that in isolated cases of this disease there is a risk of mosaicism, resulting in genetically different cell lines in the same or different tissues. Because of this consideration, in a subsequent pregnancy, prenatal diagnosis was performed on the mother, who was previously excluded from carrying the deletion based on DNA analysis of blood leukocytes. The examination showed the sex of the foetus to be male, and notably, a deletion identical to that in the ill boy was detected. This indicates that the patient has a germ cell deletion (germline mosaicism).
Asunto(s)
Mutación de Línea Germinal , Distrofia Muscular de Duchenne/genética , Adulto , Femenino , Heterocigoto , Humanos , Masculino , Mosaicismo , Linaje , Embarazo , Diagnóstico PrenatalRESUMEN
A search for female mutation carriers was performed in 40 families with an isolated case of Duchenne/Becker muscular dystrophy due to a deletion in the dystrophin gene. Intragenic restriction sites and microsatellite sequences (CA repeats) were analysed in females possible carriers of the deletion. Application of this approach enabled us the detection of the deletion in 19 females in 9 families and exclusion of the deletion in 41 females in 23 families. The results of DNA analysis in the remaining 8 families were not informative.
Asunto(s)
Distrofina/genética , Eliminación de Gen , Tamización de Portadores Genéticos , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Niño , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Humanos , Masculino , Repeticiones de Microsatélite/genética , Distrofia Muscular de Duchenne/epidemiología , Linaje , Mutación Puntual/genética , Polimorfismo Genético/genética , Cromosoma X/genéticaRESUMEN
Carrier/noncarrier status of the mutated dystrophin gene was established in 9 females from four families with Duchenne/Becker muscular dystrophy, in which samples of DNA from the affected members were not available. Analysis of extra- and intragenic polymorphic segments of the dystrophin gene enabled identification of two female carriers and exclusion of carriership in four females. In three cases the results were not informative because of recombination in the analysed segment of the gene.
Asunto(s)
Distrofina/genética , Tamización de Portadores Genéticos , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Mutación Puntual/genética , Alelos , Análisis Mutacional de ADN , Femenino , Eliminación de Gen , Pruebas Genéticas , Humanos , Masculino , LinajeRESUMEN
Studies on the mutation 563T and silent mutation 1311T of the glucose-6-phosphate dehydrogenase (G6PD) gene in Poland were performed in 26 families affected with G6PD deficiency classified-according to WHO-as group 2 G6PD deficiency. Both mutations were found in 19 families, including 17 of Polish origin. Mutation 563T alone was found in 1 Greek female. The frequency of the silent mutation 1311T in Polish unaffected controls was 0.10. It is postulated that at least parts of the Polish (or Middle-Eastern European) and Mediterranean populations are of a common origin.
Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa/genética , Mutación , ADN/análisis , Eritrocitos/enzimología , Favismo , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/etnología , Humanos , Masculino , Polonia/epidemiología , Reacción en Cadena de la PolimerasaRESUMEN
DNA analysis was performed in 190 cases of Duchenne and Becker muscular dystrophies (DMD/BMD), including 150 cases with DMD and 40 cases with BMD, using Southern blotting and PCR multiplex techniques with application of 25 pairs of primers. Deletions in the overall material were found in 109 cases: 81 (54%) in patients with DMD and 28 (70%) in patients with BMD. All the deletions in DMD were out of frame with the exception of two cases, whereas in BMD all the deletions but two were in frame. Junction fragments were detected in 12 cases of DMD. In five cases duplications were found: four in patients with DMD and one in a patient with BMD.
RESUMEN
RFLP polymorphism and the sequence of repeated CA were analysed by means of polymerase chain reaction in 62 families in which cases of DMD/BMD had occurred. The established carriers were suggested to undergo prenatal examinations for avoiding giving birth to a child with Duchenne or Becker type of muscular dystrophy.
Asunto(s)
Distrofina/genética , Tamización de Portadores Genéticos , Distrofias Musculares/genética , Mutación Puntual , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Factores Sexuales , Cromosoma XRESUMEN
Arylsulfatase A (ASA) pseudodeficiency (Pd) was defined as the in vitro measurement of low enzyme activity in a healthy person. A variable incidence of the Pd allele was found in different populations; it was 10-20 times higher than that of metachromatic leukodystrophy (MLD). In Poland we estimated the incidence of the Pd allele at 6% and that of isolated 1788 mutation (loss of glycosylation site) at 3%. Out of 8 cases with neurological symptoms and low ASA activity, 2 were found to be homozygous for the Pd allele; 2 MLD patients had healthy siblings homozygous for the Pd allele and another patient's allele bore two mutations, Pd and that causing MLD.
Asunto(s)
Cerebrósido Sulfatasa/deficiencia , Frecuencia de los Genes , Leucodistrofia Metacromática/epidemiología , Leucodistrofia Metacromática/genética , Alelos , Heterocigoto , Homocigoto , Humanos , Leucodistrofia Metacromática/enzimología , Polonia/epidemiologíaRESUMEN
54 patients from 45 families were examined one to twelve years after the hospitalization in the Department of Neurology in Warsaw in period between the years 1980 and 1992. The diagnosis of the limb-girdle muscular dystrophy (LGMD) was established, or seriously considered during the first examination. Presently verification of the diagnosis is performed on the basis of DNA analysis and muscular dystrophin assessment. In 14 cases dystrophinopathy was revealed: 13 patients with Becker muscular dystrophy (BMD) and one female manifesting carrier. This examination is of great importance for genetic counselling and for correct diagnosis of sporadic male cases and girls manifesting carriership.
Asunto(s)
Distrofias Musculares/genética , Adolescente , Edad de Inicio , Anticuerpos Monoclonales , Niño , Preescolar , Cromosomas Humanos Par 21 , ADN/análisis , Femenino , Eliminación de Gen , Humanos , Cariotipificación , Masculino , Cromosoma XRESUMEN
We have cloned and sequenced the two intervening transcribed spacers in the rDNA repeat unit of three Aspergillus species--A. nidulans, A. awamori and A. wentii. The A. wentii and A. awamori spacers are almost identical and share a high degree of homology with the A. nidulans spacers. All spacers have a high G-C content (66%-76%) and the potential of forming complex secondary structures, which may indicate that they play a role in the maturation of pre-rRNA molecules.
Asunto(s)
Aspergillus/genética , Evolución Biológica , ADN Ribosómico , Secuencia de Bases , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Secuencias Repetitivas de Ácidos Nucleicos , Homología de Secuencia de Ácido NucleicoRESUMEN
DNA was isolated and analysed in 96 patients with Duchenne or Becker muscular dystrophy (DMD, BMD); 9 of them were affected with BMD. Delections were found in 60 Patients (62.5%) using six cDNA probes. In some cases the PCR technique was also applied. In patients with BMD all deletions but one were in frame and involved exons 45-54. On the contrary, most deletions in DMD were out of frame and varied in their location. In five families prenatal diagnosis was carried out.
Asunto(s)
Distrofina/genética , Eliminación de Gen , Distrofias Musculares/genética , Cromosomas Humanos Par 21 , Distrofina/aislamiento & purificación , Exones/genética , Femenino , Humanos , Masculino , Distrofias Musculares/diagnóstico , Distrofias Musculares/enzimología , Diagnóstico Prenatal , Cromosoma XRESUMEN
DNA analysis was carried out in 113 patients of 103 families. In 58 families (55%) deletions were found using different cDNA probes. The attempt of studying the correlation between mental retardation in patients and the exon deletions was made. Dystrophin was evaluated in 80 patients including 12 affected females. One girl had chromosomal translocation X;22 and was a true DMD case. An unusual pedigree typical of X-linked transmission with affected subjects showing clinical features of DMD but with normally expressed dystrophin is presented. Owing to DNA and dystrophin analysis the correct diagnosis in some doubtful cases of muscular dystrophies could be established and some unusual pedigrees detected.