摘要:

By using chemical cleavage mismatch analysis and the single strand conformation polymorphism technique, DNA fragments of the apo CIII gene, including the 5′ flanking region and all the exons, were screened for sequence changes underlying the observed association between familial combined hyperlipidaemia (FCHL) and the apo AI‐CIII‐AIV gene cluster in affected individuals from eight FCHL families. A C1100‐T transition in the wobble position of codon 14 in exon 3 and a T3206‐G transversion in the non‐translated region of exon 4 were identified, occurring in four and all probands, respectively. Using these variants and the G_75‐A transition in the apo AI promoter, co‐segregation of the gene cluster with hyperlipidaemia could be excluded in all eight families (lod score ‐∞ at θ=0). No support for co‐segregation was obtained using the affected pedigree member method of linkage analysis (overall T=–0.77 for f (p)=1√p). The frequencies of T1100and G3206in a group of 55 patients with combined hyperlipidaemia were 0.35 and 0.52, respectively, which were significantly higher compared to 360 controls (0.21, p<0.01 and 0.35 p<0.005 respectively). In patients homozygous for the T1100allele, levels of plasma triglyceride were 2.5‐fold higher (868 mg/dl) than those homozygous for the C1100allele (337 mg/dl), while patients heterozygous for the polymorphism had intermediate values (443 mg/dl) (p<0.01). A similar association was seen in controls (p<0.04). The three polymorphisms studied were in strong linkage disequilibrium in both the group of CHL patients and the unrelated individuals. This study confirms the association between common variation in the gene cluster and differences in plasma lipid levels in the general population and in patients with combined hyperlipidaemia, but fails to confirm co‐segregation with FCHL, suggesting the role of other genetic or environmental fa

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04404.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A total of 140 South African (SA) Caucasoid cystic fibrosis (CF) families were analysed for the common CF mutation, ΔF508. The 52 non‐ΔF508 CF chromosomes in a subset of 127 of these families were also tested for 39 other known CF mutations. The most frequent mutation, apart from ΔF508 (which occurs at a frequency of 79%), was G542X (1.3%). Four other mutations, R553X, S549N, 621 + 1G→T and N1303K, were each found in single families. The other 35 mutations remained unidentified in this sample of CF families. Since 83% of SA Caucasoid CF mutations have been identified, diagnosis by mutation analysis will be possible in only 69% of CF cases. When a diagnosis has been confirmed by a positive sweat test, a combination of linked marker analysis and mutation detection will be necessary if prenatal diagnosis and carrier detection are to be offered in the remaining fa

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04405.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We have examined 48 Danish families in which malignant hyperthermia reactions have occurred, with respect to three of six published mutations in the gene for the calcium release channel of sarcoplasmic reticulum (the RYR1 gene) believed to cause malignant hyperthermia susceptibility in man. The mutations are Arg614Cys, also known as the “pig mutation”; Arg163Cys; and Ile403Met. The only mutation found was Arg163Cys, which was detected in only one family. The results of this study indicate that other mutations must underlie the disorder in most Danish malignant hyperthermia‐susceptible families, and that the “pig mutation” is not a frequent cause of malignant hyperthermia susceptibility i

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04406.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A population‐based register of all autosomal trisomies diagnosed in Scotland was established in 1989. Data were provided by all cytogenetic service laboratories, and included karyotype, date and place of outcome, indication for analysis, maternal age and place of residence. The Register includes all foetuses diagnosed prenatally and all cytogenetically‐confirmed live‐ and still‐births with autosomal trisomy, including partial, mosaic and familial cases. In the 2 years 1989‐90, 76 prenatal and 147 postnatal diagnoses were notified. For Down syndrome karyotypes the estimated rate, assuming no terminations and after adjusting for spontaneous foetal losses following diagnosis, was 1.23 per 1000 livebirths. This was almost identical to that expected by applying published maternal age‐specific rates to the maternal age distribution in Scotland, indicating a very high level of ascertainment. The adjusted rates for trisomies 13 and 18 were also close to expected values derived from published data. Prenatal screening was estimated to reduce the newborn incidence of trisomy 21 by about one quarter overall, and about one half in mothers over 35 years. For trisomy 18, the estimated overall reduction was also about one quarter. It is concluded that the Register provides a practical and cost‐effective means of monitoring the effects of prenatal screening, with near‐complete ascertainment. In the longer term it will provide a database for studies of the actiology of t

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04407.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The sequential changes of Lp(a) lipoprotein concentrations in patients (n=59) suffering acute myocardial infarction (AMI) were examined and compared with other plasma proteins. The temporal and quantitative characteristics of the responses in concentration of acute phase reactants (CRP, haptoglobin, α1‐antitrypsin, α‐acid glycoprotein), lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol) and apolipoproteins AI and B were similar to previous reports. Lp(a) lipoprotein showed transient changes with an initial decrease of 10–25% compared to the 3‐month control value, followed by rebound on day 7–11 above admission level, before again declining. We were able to demonstrate a quantitative relationship between infarct size and alterations in plasma levels of acute phase reactants. However, in addition to rather unusual significant fluctuations during AMI, Lp(a) lipoprotein changes seemed unrelated to infarct size. These findings do not support the view that Lp(a) lipoprotein acts as an acute pha

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04408.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Two Turkish sibs with clinical features of Ehlers‐Danlos syndrome type VI‐B are presented. The hydroxylysine contents of dermis and gel electrophoresis of type I and type III collagen produced by fibroblasts were normal. Ultrastructural studies of skin collagen and elastic fibers showed discrete abnormalities. Other syndromes with similar clinical, biochemical and ultrastructural features are discus

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04409.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We report one patient with ade novoinversion duplication 18 (ptercen) and two cases of direct tandem duplication 18 (ptercen), one due to maternal inheritance and the other arising as mosaicism of unknown origin. The duplications are demonstrated by high resolution banding. They were verified byin situhybridization with a paint specific for chromosome 18 and with DNA probe LI.84 specific for the centromere region of chromosome 18. FISH with the genomic DNA probe pHRR68 specific for 18p11.32 revealed a subtle deletion concomitantly involved in the case of inversion duplication 18p. The patients exhibit slight developmental delay/moderate mental retardation and only a few dysmorphic features. The literature on trisomy 18p is reviewed and the present cases are compared to it.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04410.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A single mandibular incisor and an unusually narrow mandible and tongue were noted in an 8‐year‐old moderately retarded boy with 18p‐ (45, XY, der dic (18) (18qter‐p11.2::22p 11.2‐qter). While a single maxillary incisor, considered a minor feature of holoprosencephaly, was reported in three cases of 18p‐, reduction of mandibular incisors has been a very rare finding and has never been noted in si

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04411.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We have examined healthy Norwegians with respect to two restriction fragment length polymorphisms at the locus for atrial natriuretic factor, detectable with the restriction enzymes XhoI and BglI, respectively. No association with systolic or diastolic blood pressure level or variability was found. Thus, the normal genes detected by examination of these restriction fragment length polymorphisms have neither “level gene” nor “variability gene” effects on normal blood p

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04412.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We have studied a normal restriction fragment length polymorphism at the renin locus, detected with the restriction enzyme BgII in healthy Norwegians. No association with blood pressure level or variability was found. Thus, the normal genes detected by examination of this restriction fragment length polymorphism at the renin locus have neither “level gene” nor “variability gene” effects on normal blood p

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04413.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY