摘要:

The lipoprotein Lp(a) is associated with increased risk of atherosclerosis and myocardial infarction in humans. Lp(a) is mostly confined to primate species, due to the limited phylogenetic distribution of its distinguishing protein component, apolipoprotein(a) which is a close homolog of plasminogen. The known properties of Lp(a) are reviewed here. Many of these derive from the ability of Lp(a) to bind to the same substrates as plasminogen. A possible new animal model of Lp(a) is the hedgehog, which contains an Lp(a)‐like particle that is the apparent product of independent evolution of a multi‐kringle, apolipoprotein(a)‐like protein by duplication and modification of portions of the hedgehog plasminogen

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03281.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A plethora of different mutations in the gene for the low density receptor (LDLR) are responsible for the autosomal dominant inherited disorder familial hypercholesterolemia (FH). However, only a few splice site mutations have been identified in this gene. We here report a defect presumably affecting the splicing of precursor mRNA, resulting from a novel mutation, a G to A transition at the terminal nucleotide of intron 12, of the LDLR gene detected in three unrelated families with heterozygous FH. This mutation markedly reduced the steady‐state transcript level of the mutant LDLR allele as compared to the corresponding normal LDLR allele in heterozygous FH patients as measured by a fluorescence based, allele‐specific quantitation technique. In the FH families, the acceptor splice site mutation cosegregates with hypercholesterolemia, and it is associated with onset of ischemic heart disease in the fifth and sixth decade of l

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03282.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In our investigation of the LDL receptor gene in 30 Spanish patients, who were clinically diagnosed as heterozygous FH and were unrelated, we have applied single strand conformation polymorphism (SSCP) analysis and solid‐phase sequencing. We identified two novel pathogenic mutations accounting for one third of the FH in this patient sample. Six patients were found to have a G to T substitution at nucleotide position 91 in exon 2 that results in a stop codon, E10X. Four patients were found to have a G deletion at nucleotide 518 in exon 4, causing a translational frameshift and a stop codon, 518delG. We have developed two polymerase chain reaction (PCR) based assays to detect easily these two mutations in all the available family members. We found fourteen E10X mutation carriers and eighteen 518delG mutation carriers. There was no statistically significant difference in mean lipid levels between carriers of these two mutations. Furthermore, haplotype analysis revealed that all E10X mutation carriers had the allele determined by TaqI‐, Stul+, Avall+, Ncol‐ and all 518delG mutation carriers had the haplotype TaqI‐, Stul+, Avall‐, NcoI+. This indicates that both mutations may have been inherited from common ancestors, res

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03283.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Malignant hyperthermia (MH) is a pharmacogenetic disorder. Susceptibility to MH (MHS) is presumed to be inherited in an autosomal dominant way. MH crises are triggered by halogenated inhalational anaesthetics and suxamethonium, and may be lethal if not treated early and adequately. Until now, eight mutations in the RYR1 gene have been described as causes of MHS phenotype in various MH families The mutation RYR1 G1021A (Gly341Arg) has been reported to account for approximately 10% of Caucasian MHS cases. However, in our study this mutation was discovered in only 1 out of 89 Scandinavian families, indicating that this mutation may be the cause of MHS in only about 1% of MHS families in those populations. The mutation may have been brought to Scandinavia by an immigrant.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03284.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

X‐inactivation has been studied in a series of monozygotic female twins and their female relatives by a PCR method which detects methylation at the androgen receptor locus (HUMARA). The results obtained are compared to those from an earlier study employing probe M27β which detects locus DXS255. Analysis of X‐inactivation in girls with Rett syndrome and their mothers by four different methods did not indicate a direct relationship between non‐random inactivation of the X‐chromosome and the presence of the disease with the exception that any skewing detected in the probands tended to favour the preferential inactivation of the paternally inherited X‐chromosome. No evidence for the involvement of uniparental disomy in the etiology of the disease

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03285.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis byin situhybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti‐CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti‐alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied byin situhybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03286.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The aim of the current study was to assess the psychological and social impact of ΔF508 carrier screening for cystic fibrosis among pregnant women. The impact of carrier screening was assessed in terms of anxiety, perception of health, reproductive decisions, retention of results, and sharing of information with relatives by two self‐administered questionnaires sent to 160 women with a positive and 200 women with a negative test result. While no attempt was made to make women accept or decline testing, 22–28% of those tested found it difficult to reject the test when offered. Women with a positive test result became more anxious than did women with a negative result. However, their perception of future health did not change. Most carriers shared the information about their result with relatives and friends. Carriers had the best retention of pretest information and test result, although a third of the carriers believed that they could not have a child with cystic fibrosis when the partner's test for ΔF508 and five other mutations were negative. Most women with a negative test result did not remember their result correctly a year after testing. Few women with a positive result changed their reproductive plans because of the result of the

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03287.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A 31‐year‐old female is reported with mild to moderate mental retardation, facial dysmorphy, congenital cardiopathy, and mild thrombocytopenia as the most important clinical findings. Chromosome analysis in lymphocytes showed ade novodir dup (11)(q13.3→14.2), by both G‐banding and FISH techniques. Previously reported constitutional duplications of 11q are mostly the result of unbalanced translocations involving chromosome 11q, and are associated with a partial monosomy or trisomy of the translocation partner chromosome. In case of an unbalanced translocation it is not clear which clinical findings result from the chromosome 11 duplication and which result from the abnormality on the translocation partner chromosome. This is the first report on a constitutional duplication of chromosome region 11q13.3→14.2 without involvement of other ch

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03288.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Hydrolethalus syndrome consists of hydrocephalus, polydactyly, micrognathia, midcranial malformations, visceral abnormalities and perinatal lethality. It was first described in Finland, and only a few other cases outside Scandinavia are known. We report the first Hungarian patient who displayed many signs of the syndrome but had no cleft lip and visceral abnormalities. This observation suggests the existence of oligosymptomic hydrolethalus syndrome, and suggests that Dandy‐Walker malformation with polydactyly may be a manifestation of the hydrolethalus syndrom

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03289.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

After ultrasound diagnosis of a fetus with severe hydrocephalus and Dandy‐Walker malformation, amniocentesis revealed chromosomal mosaicism for dup(1q) and del(Xq). The neonate had dysmorphic facial features, vertebral abnormalities, and pulmonary hypoplasia, and expired shortly after birth. This report confirms the poor prognosis reported for partial trisomies involving the long arm of chromosome number

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03290.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY