摘要:

The effect of variation at the cholesteryl ester transfer protein (CETP) gene locus and in the apolipoprotein (apo) AI‐CIII‐AIV gene cluster on the susceptibility of individuals with non‐insulin‐dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 136 male and 122 female patients with NIDDM. The prevalence of myocardial infarction was high (38%) in patients with the EcoNI genotype 2–2 of the CETP gene locus (= 2‐2; subjects homozygous for the absence of the restriction site) compared with patients with the genotype 1–1 (=1–1; subjects homozygous for the presence of the restriction site) (18%, p<0.02). The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was high in 2–2 (73%) compared with the genotype 1–2 (= 1–2; heterozygous for the presence of the restriction site) (52%, p<0.02) and genotype 1–1 (p = 0.06). CHD was more prevalent in men with 2–2 (70%) than in those with 1–1 (42%, p<0.05), but in women no significant differences were found in the prevalences of CHD between the EcoNI genotypes. Neuropathy was more often present in the patients with 2–2 (31%) than in those with 1–1 (12%, p<0.02) or 1–2 (14%, p<0.01). Plasma total cholesterol and total‐ and VLDL‐triglycerides were higher in women with the EcoNI genotype 1–1 than in those with the genotype 1–2. In men no significant differences in plasma lipids were found. In addition, the prevalence of cerebrovascular disease was high (21%) in the patients with the genotype 1–1 of the TaqlB polymorphism compared with the genotype 2–2 (6%, p<0.0–2). None of the alleles defined by four polymorphisms in the apo AI‐CIII‐AIV gene region were associated with an increased risk for macroangiopathy. The PstI polymorphism had an effect on plasma triglyceride levels. At the CETP locus one pair of loci (TaqlB and EcoNI) and three pairs of loci at the apo AI‐CIII‐AIV gene cluster (SacI and MspI, SapI and PvuII and MspI and PvuII) showed significant allelic association. In conclusion, the variation of CETP locus modulates the risk for diabetic complications in patients with NIDDM and the effect seems to be different between men and women. In contrast, the AI‐CIII‐AIV gene cluster polymorphisms seem not to be related to the risk of CHD in NIDDM. Long‐term follow‐up studies are needed to confirm the as

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04230.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Atopy, characterised by allergic asthma and rhinitis, is due to increased IgE responses to common aeroallergens. An Oxford group has described maternal inheritance of atopy, where there is significant linkage between IgE responsiveness and a VNTR marker D11S97 and a CA microsatellite within a candidate gene, the high affinity IgE receptor β subunit(FcεRIβ), on chromosome 11q. Attempts at independent replication have produced conflicting results. We therefore recruited 270 atopic asthmatic probands in a Japanese community population for genetic linkage analysis. Four families, each with more than 15 meioses and a clear phenotype for atopy, were selected for genetic analysis. Atopy was defined as presence of all of raised total IgE, positive RAST and skin tests to three or more aeroallergens; non‐atopy, as absence of all these criteria. Linkage analysis showed a maximum two‐point lod score of 9.35 for D11S97 and FcεRIβ under the assumption of unequal rates of maternal and paternal recombination. Two families showed close genetic linkage with FcεRIβ with a pattern of maternal inheritance. These results from a Japanese population provide further evidence for genetic linkage between severe atopy and chromosome 11q13 and the likelihood of genomic imprinting at

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04231.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

One of the primary goals in medical genetics is a precise clinical definition of chromosomal diseases. This is now possible because of the increased number of case reports and new techniques. A male patient, without a clear‐cut syndrome, was cytogenetically investigated. Chromosomal analysis showed a small unidentified bisatellited supernumerary marker.In situhybridization with a biotin‐labeled DNA probe for the chromosome 15 centromere (D15Z1) demonstrated that the marker was derived from chromosome 15. Hybridization with the Prader‐Willi Syndrome Cosmid biotinylated probe (localized to band 15q11‐q13) showed a signal on both ends suggesting a marker with a symmetrical inv dup(15) and a breakpoint localized in q13. It was then possible to define the karyotype as: 47,XY,+ inv dup(15) (pter‐q13::q13‐pter). All cases of inv dup(15) reported in the literature were reviewed, paying particular attention to the different breakpoints involved, in order to provide a better clinical definition of th

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04232.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

From 1980 to 1991, 6.3% of the adult population of the province of Sassari, Northern Sardinia, underwent voluntary β‐thalassemia screening. Of the 28 000 subjects examined, 15.7% proved to be heterozygotes for β‐thalassemia. In addition, the screening of 7500 students in 26 villages in Sassari province fixed the frequency of β‐thalassemia in this part of Sardinia at 10.4%. Of the 539 couples at risk to be expected from this figure, the screening detected 43% (234). The data suggest that inductive screening played a major role in the efficiency of this preventive β‐thalassemia program. Follow up of 221 pregnancies found to be at risk for homozygous β‐thalassemia and referred to the Antenatal Diagnosis Service, Cagliari, Southern Sardinia, showed that antenatal diagnosis was carried out in 80% of them. The overall percentage of couples refusing antenatal diagnosis was 10.8%, but over the years the acceptance rate for the procedure increased from 87% to 96%. Atypical hematological findings in 1.5% of 468 members of the couples at risk required globin chain synthesis and molecular analyses to define the precise β‐thalassemia genotype. Heterogeneous “mild”β‐thalassemia mutations as well as coexisting δ‐thalassemia were found in silent type I and type II β‐thalassemia carriers which, without chain synthesis and DNA investigations

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04233.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Cytogenetic study of a 3‐year‐old girl with developmental delay and some minor abnormalities revealed a complex chromosome rearrangement (CCR) involving seven chromosomes with eight breakpoints, leading to monosomy of segment 5q15‐q22. According to breakpoint distribution, CCRs may be classified as those with primary intrachromosomal abnormalities (including inversions, insertions, duplications, etc.) and those without them. Only the latter group of CCRs was used in this analysis. Comparison of theoretical and observed breakpoint distributions in 33 cases demonstrated that recurrent involvement of some chromosome(s) (“re‐entry”) occurs more frequently than expected. One possible explanation for this observation suggests that the initial event leads to an unstable provisional rearrangement, and subsequent breaks are necessary to stabilize th

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04234.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Genetic polymorphisms of apolipoprotein (apo) A‐IV have been shown to influence lipoprotein metabolism in some human populations. In this study, we have evaluated the physiological effect of three apo A‐IV polymorphisms (Gln360‐

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04235.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Two of the 13 PCR markers were most informative in tentatively identifying a major gene for cleft lip on the q arm of chromosome #4 with a maximum LOD score of 2.27 (Ø= 0

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04236.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Holt‐Oram syndrome is an autosomal dominant disorder with congenital heart defects and skeletal malformations of the upper extremities. A patient with a deletion of 14q23‐24 and Holt‐Oram syndrome has been described. In this report, however, genetic linkage to the 14q23‐24 region is excluded in a multigeneration family with five available individuals affected with Holt‐Oram syndrome. Familial Holt‐Oram syndrome might be different from the syndrome with the 14q23

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04237.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X‐linked KS, and one with X‐linked KS and X‐linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney. In addition, two pedigrees had males who died in the neonatal period with bilateral renal agenesis. Only two of the four affected individuals in the family with X‐linked KS and X‐linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite all four patients demonstrating an interstitial deletion within the short arm of the X‐chromosome. These data indicate that unilateral renal agenesis is much commoner than previously suspected in patients with X‐linked Kallmann's syndrome, but that it may have incomplete penetrance wi

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04238.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The usefulness of intragenic restriction fragment length polymorphisms (RFLPs) for Bc1I, HindIII and XbaI, adapted for polymerase chain reaction (PCR), was tested for the detection of haemophilia A carrier status in the consultand of a family in which only haematological information was available on the inheritance of the trait. Hair follicles were used as the non‐invasive source of DNA. The mother was found to be homozygous for Bc1I and heterozygous for HindIII sites, whereas her status as regards informativeness could not be established for XbaI. On the basis of HindIII RFLP, the daughter was found to be a carrier of the haemophilia trait. This was confirmed by sequencing the amplified intron 19 of the mother and the daughter. The RFLP for XbaI did not appear to be suitable for carrier detection using PCR due to the difficulty of establishing homozygosity or heterozygosity from the results of digestion of the amplified produc

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04239.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY