摘要:

We studied the influence of selected genetic markers on the intra‐individual long‐term variability in serum lipid levels. The study cohort consisted of a sub‐sample from a large follow‐up study of atherosclerosis precursors in children and young adults. A total of 320 subjects had determinations of apo B XbaI RFLP genotypes, 305 subjects had apo AI/CIII SstI RFLP genotype determinations and 1581 subjects had their apo E phenotypes determined. Complete data on serum lipids were available at 3‐year intervals over a 6‐year follow‐up period. The subjects were healthy and aged 3–18 years at baseline. Intra‐individual variability was assessed with a nested analysis of variance procedure. Each of the genetic markers studied here significantly affected intra‐individual variability of serum lipid levels. No clear sex influence was observed, although the differences in variability tended to be more significant in males. Apo B XbaI genotypes significantly influenced intra‐individual variability of total and LDL‐cholesterol levels in both sexes. A marked effect of the XbaI geno‐type was also found on triglyceride variability. In males the standardized intra‐individual triglyceride variances were 0.71 and 0.34 in genotypes X1X1 and X2X2, respectively (p<0.001), with a clear gene dosage effect. The apo AI/CIII genotype had an influence only on the variability of total cholesterol and LDL‐cholesterol levels and only in males. The apo E phenotypes were associated with intra‐individual variability in total and LDL‐cholesterol levels but again, only in males. The lowest variability was observed in the phenotype E4/3 where high mean values were also observed. We also examined the effect of combined genetic markers. Up to 7 times greater variability was found in the combination E3/2 + S1S1 compared to combination E4/3 + S1S2 (p<0.001). In addition, mean levels of, e.g., LDL‐cholesterol were 70% greater in the combination of E4/3 +S1S2 compared to E3/2 + S1S1. This implies that subjects with both these genetic markers have high LDL‐cholesterol values that also tend to remain constantly elevated. In conclusion, it is evident that many of the presently known DNA polymorphisms of the coronary heart disease candidate gene loci also influence intraindividual variability of serum lipid or lipoprotein levels. These findings can be used to further refine our ability to predi

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04007.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of α1‐antitrypsin (P<0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P<0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase‐inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P<0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of α1‐antitrypsin differs in various ethnic groups and may play a role in

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04008.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The Charcot‐Marie‐Tooth (CMT) syndrome comprises a heterogeneous group of disorders affecting the peripheral nerves and anterior horn cells of the spinal cord. They constitute a significant proportion of the burden of disability caused by single gene neurological disorders, with a disease prevalence of 16.7 per 105of the South Wales adult population. The clinical and genetic characteristics of these diseases in the population are described. In those cases identified as type I hereditary motor and sensory neuropathy (HMSN I), we have shown that it is possible to correlate disease severity with age, and that there is no clinical evidence for imprinting, manifest either in age of onset or disease sever

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04009.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Molecular diagnosis of cystic fibrosis (CF) in the Italian population, based on the detection of the deltaF508 mutation (51.2% of CF chromosomes), provides full informativity for prenatal diagnosis (PDN) in about 28% of families at risk. Identification of the predominant non‐deltaF508 mutations allows the characterization of about 70% of CF chromosomes, making approximately 48% of couples fully informative. In families where at least one chromosome remains uncharacterized, allele segregation is still determined using RFLPs closely linked to the CF gene. The recent identification of three polymorphic clusters of dinucleotide repeats (IVS8/ GT, IVS17b/TA and IVS17b/CA) led us to evaluate whether their analysis might improve feasibility studies for prenatal diagnosis or hetero‐zygote identification. One hundred nuclear families with a CF child, reflecting the general Italian deltaF508 mutation distribution, were geno‐typed for the three microsatellites. In this study microsatellite analysis using IVS8/GT and IVS17b/TA allowed the identification of both parental CF chromosomes in 94% of couples; inclusion in the study of the less polymorphic repeat locus, IVS17b/CA, slightly improved this percentage (97%). Hence, a strategy involving primarily the detection of the delta F508 mutation and secondarily microsatellite analysis makes possible PDN of CF in virtually all Italian CF fam

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04010.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Van Maldergem et al. (1992) described a new syndrome in an 11‐year‐old girl, characterized by: mental retardation, hypotonia, dysmorphic facies with telecanthus, epicanthus, broad flattened nose, large inverted W‐shaped mouth, malformed ears, finger camptodactyly, and joint hyperlaxity. In this report we present a 5‐year‐old girl with very similar clinical findings. We confirm the existence of this condition as an independent clinical entity, and we propose that, based on the major clinical manifestations, it should be defined as “cerebro‐facio‐arti

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04011.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Gene localization was determined by linkage analysis in a large French family with X‐linked mental retardation (MRX). Seven living affected males were clinically studied and the clinical picture was characterized by moderate to severe mental handicap with poor secondary speech acquisition. Seizures, slight microcephaly, simian crease, anteverted pinnae, and macroorchidism were observed in some patients only. Linkage analysis revealed no recombination between the MRX gene and two loci: DXS255 at Xp11.22 (Zmax = 3.31 at θ= 0.00) and PGKP1 at Xq11.2‐q12 (Zmax = 3.08 at 9 = 0.00). One recombination was observed between the gene and the two loci DXS164 at Xp21.2 and DXS441 at Xq13.3, respectively. These results suggested gene localization in the pericentromeric region of the X chromosome, and the LOD scores justified assignment of the symbol MRX14 to this fa

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04012.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We report on two boys with oto‐palato‐digital syndrome type II, characterized by growth retardation, bowed long bones, missing or hypoplastic fibulae, sclerosis of the skull base and wavy, irregular clavicles and ribs. The facial appearance is distinctive due to prominent forehead, widely spaced eyes, antimongologid slant of palpebral fissures, flattened nasal bridge and retrogenia. The mother of one patient showed a mild manifestation of oto‐palato‐digital syndrome type II. Only about 20 cases of this rare X‐linked disorder have been reported so far. The similiarities and dissimilarities to oto‐palato‐digital syndrome type I

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04013.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04014.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04015.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY