摘要:

One hundred and forty sibships consisting of 280 brothers and 256 sisters with a family history of myocardial infarction were investigated for the possible involvement of a major gene in the determination of LDL‐C, Apo‐B and LDL‐C/Apo‐B ratio (as a surrogate for LDL subclasses). The mean ages were 29.5 years (range 15–48) and 29.2 years (range 15–47), for brothers and sisters, respectively, and values were initially adjusted for age effects through multiple regression analysis. Results from commingling analysis indicated that for LDL‐C a single normal distribution fitted the data as well as a mixture of two distributions. For Apo‐B, a mixture of two normal distributions fitted the data significantly better than a single distribution (χ2= 7.8, df = 2, p = 0.02). For LDL‐C/Apo‐B ratio a mixture of three normal distributions fitted the data significantly better than two distributions (χ2= 9.2, df = 2, p = 0.01). A regression analysis applied to the logarithm of the sex‐and age‐adjusted mean and variance within sibship, showed no indication of a major gene involvement for LDL‐C. For Apo‐B and LDL‐C/Apo‐B ratio, mere existed, however, significant linear relationships between the logarithmically transformed means and wimin sibship variances which support the involvement of major genes. In addition, the Bartlett test applied to the data of within‐sibship variances also rejected the null hypothesis of multifactorial transmission for Apo‐B and LDL‐C/Apo‐B ratio (p<0.0001). Lastly, the results from sib‐pair linkage analyses provided significantly positive evidence for linkage between ApoB

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02338.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Autosomal dominant polycystic kidney disease (ADPKD), is a heterogeneous disorder, primarily characterized by the formation of cysts in the kidneys, and the late development in life of progressive chronic kidney failure. Three genes are implicated in causing ADPKD. One on chromosome 16, PKD1, accounts for 85–90% of all cases, and the PKD2 gene on chromosome 4 accounts for the remainder. A very rare third locus is still of unknown location. We used PKD1‐and PKD2‐linked polymorphic markers to make the diagnosis of ADPKD in young presymptomatic members in affected families. We showed that in young members of families where clinical diagnosis cannot be definitively established, molecular linkage analysis can assist clinicians in the diagnosis. In one family a 24‐year old had one cyst on the right kidney; however, molecular analysis showed clearly that he had inherited the normal haplotype. In another family, in one part of the pedigree there was co‐inheritance of the disease with a PKD1‐linked haplotype which originated in a non‐affected 78‐year‐old father. Analysis with PKD2‐linked markers excluded this locus. The data can be explained in one of two ways. Either this family phenotype is linked to a third locus, or the proband was the first affected person, most probably because of a novel mutation in one of her father's chromosomes. In conclusion, the combined use of markers around the PKD1 and the PKD2 locus provides more definitive answers in cases where presymptomatic diagnosis is requested by

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02339.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We report here on phenotype‐karyotype correlations in two patients with and without complete features of the WHS but sharing the lack of a specific cosmic probe (D4S96/D4Z1) from 4p16.3. These findings indicate that WHS is true a contiguous gene deletion syndrome in nature and expressio

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02340.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Screening for cystic fibrosis (CF) has been offered to pregnant women seeking chorionic villus sampling (CVS) for prenatal chromosomal abnormality investigation. The mutation panel has increased over the years to include 8 mutations and can detect 65% of abnormal CF genes in the Italian population. Testing was offered to a total of 2214 consecutive pregnant women; 45 of them declined screening (take up rate: 98%). In 1055 of the 2169 pregnancies screened, the test was at first done on the fetus, while in the remaining cases both parents were investigated. Among parents 46 carriers were identified (2.1%), in 41 of whom the mutation was delta F508. In two couples both parents were heterozygous, and in one the fetus was affected and the pregnancy was terminated. Although CF testing offered to pregnant women undergoing invasive investigation such as CVS may not be the model for a mass screening, its very high effectiveness can represent an advantageous component of more comprehensive strategies.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02341.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis ofBgtII digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls.Hindi, Avail, PvuII,MspI, andNcoI are the most polymorphic sites with individual PIC values higher than 0.28, whereas theTaqI andStuI sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH‐families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B‐100 (FDB) due to the apoB3500mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populati

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02342.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Shed deciduous teeth from patients with tuberous sclerosis, cerebral palsy, Down syndrome, phenylketonuria and healthy persons were examined with a surface microscope. We found enamel pits in all 87 deciduous teeth from the 20 patients with tuberous sclerosis, but in none of the 253 deciduous teeth from 142 controls constituting patients with cerebral palsy, phenylketonuria and Down syndrome as well as healthy persons. Enamel pits always occurred in the facial surface of the central incisor, lateral incisor and canine, while the number of enamel pits in the other surfaces of the deciduous teeth varied from none to nine. Ground sections examined microscopically revealed an undisturbed pattern of incremental lines (Retzius striae) surrounding the pits. In five dental sacs from patients with tuberous sclerosis, microscopic examination showed that the inner surface of the operculum was remarkably more irregular than in control patients.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02343.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Pallister‐Killian syndrome is a clinically recognizable syndrome characterized by tissue‐limited mosaicism for an extra 12p isochromosome. Very little is known about the underlying mechanism of this rare rearrangement. Microsatellite markers were studied from three fetuses with Pallister‐Killian syndrome and their parents to determine the parent of origin and the cell division yielding the additional isochromosome. In two cases the isochromosome contained the same allele(s) as a normal transmitted chromosome 12, one paternal and one maternal in origin. A third case showed inheritance of two different maternal alleles, indicating that at least one meiotic error was involved in the ultimate formation of the extra isochrom

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02344.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We report a family with two cases of severe pre‐eclampsia/eclampsia in which very high levels of Lp(a) lipoprotein were found. The serum level of Lp(a) lipoprotein is genetically determined and the Lp(a) apolipoprotein has a close homology to plasminogen. Very high levels of Lp(a) lipoprotein might interfere with the fibrinolytic/thrombolytic process in man. A previous report suggested that a high maternal serum Lp(a) lipoprotein level can cause fetal growth retardation, and it is proposed that very high levels might lead to increased deposition of fibrin in the uterine spiral arteries in pregnancy, which is central in the pathogenesis of pre‐eclampsia. If confirmed, a very high Lp(a) lipoprotein level could be one risk factor for pre‐eclampsia that is genetically deter

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02345.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We have screened exon 12 of the low density lipoprotein (LDL) receptor gene from 46 familial hypercholesterolemia (FH) heterozygotes and 64 normolipidemic controls for two polymorphisms,Hindi, which is caused by a T to C substitution at base 1773, and a C to T transition at base 1725, by using single strand conformation polymorphism (SSCP) analysis. Our results indicate that polymorphism at base 1725, previously reported as very rare from a Japanese sample, is quite frequent in the Spanish population and that it is closely linked to the presence of theHindisite (HincII+). Thus, both polymorphisms constitute a system of three alleles, typedHincII‐C1725,HincII+C1725, andHincII+T1725, whose frequencies in the FH sample were 0.489,0.347, and 0.164, respectively. No significant differences were found in the allele frequencies between the FH and control samples. This three‐allelic polymorphic system provides a higher information content (PIC value) than theHindiRFLP alone (0.537 versus 0.373, respectively); therefore, it is an extremely useful marker for linkage analysis of FH in Caucasian populati

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02346.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb02347.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY