摘要:

This report summarizes the results on 39 patients with Gaucher disease who have been genotyped, evaluated, and/or followed at this center. Mutation analysis for 4 common mutations; N370S, L444P, 84gg and IVS2 (+1), was performed for all patients. Mutation analysis identified both mutant alleles in 69% and at least one mutant allele in 90% of all chromosomes. This study group of 39 patients included 32 type 1, four type 2 and three type 3 patients. We include the details of the clinical course of two patients with Gaucher disease treated with enzyme replacement therapy (ERT). One patient with chronic neuronopathic Gaucher disease has been treated with enzyme replacement therapy (ERT) at a dose of 60 U/kg every 2 weeks since 2.5 years of age and has shown no progression of neurologic involvement. A second patient with non‐neuronopathic Gaucher disease has demonstrated an unusually delayed response to ERT. No clinical response was noted following 17 months of treatment at 60 U/kg every 2 weeks. Only after the dose was increased to 60 U/kg every week was a clinical response evident. Response to treatment at 15 U/kg every 2 weeks was variable in the four type 1 patients treated at the lower dose. In two of these patients with identical genotypes, one patient demonstrated a positive clinical response to low dose treatment while the other patient did no

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03268.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early‐onset Alzheimer disease, we designed a mismatched PCR‐RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR‐RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS‐1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early‐onset Alzhe

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03269.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Rothmund‐Thomson syndrome (RTS) is an autosomal recessive disorder characterized by skin abnormalities that appear in infancy, skeletal abnormalities, juvenile cataracts and other manifestations of premature aging, and a predisposition to malignancy. The diagnosis is made on clinical grounds as no consistent laboratory test has been identified. Chromosome studies have been reported for only three patients with RTS and in two of these three, trisomy 8 mosaicism was found. We performed a variety of cytogenetic and molecular genetic studies on two siblings with RTS and on their phenotypically normal parents. Two chromosomally abnormal clones involving either trisomy 8 or i(8q) were found in both patients with RTS. These clones were presentin vivo, as they were seen in interphase buccal smears and lymphocytes from unstimulated preparations using both conventional cytogenetic studies and fluorescencein situhybridization (FISH) with a centromere probe for chromosome 8. These results suggest that RTS is associated within vivoclonal chromosomal rearrangements causing an acquired somatic mosaicis

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03270.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The term Muckle‐Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities. We describe a family with nephropathy and several symptoms of MWS, but no evidence of deafness or amyloidosis. Since nephropathy without amyloidosis has never been reported in MWS, but deafness is a feature of all reported pedigrees, we conclude that members of this family have a previously unreported inherited predisposition to urticaria, arthralgia and nephropathy which is distinct from the MWS phenotyp

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03271.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Attitudes towards termination for a range of genetic conditions were studied in health professionals and lay people in three European countries: Germany, Portugal and the UK. The health professionals consisted of geneticists in all countries and additionally obstetricians from Portugal and the UK. The lay persons consisted of pregnant women, and male and female non‐medical university employees. In all, more than 1,700 study participants completed questionnaires. Overall, health professionals were more likely than the lay persons to report that they would opt for termination following diagnosis of a fetal abnormality. Differences were found between countries and study groups. German respondents were least likely to report that they would undergo termination in the case of a fetal abnormality while Portuguese respondents were most likely to report that they would undergo a termination. Further studies are needed to determine first the extent to which differences between health professionals and lay samples reflect a difference in perception of disability, including tolerance of having a child with a disability; and second, whether such differences result in health professionals presenting termination of pregnancy in a way that is not concordant with patients' value system

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03272.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Down syndrome (DS), one of the commonest causes of mental retardation in Caucasoids, has only rarely been described in Africa. In previous studies it was suggested that there may be clinical difficulties in making the diagnosis in African neonates. In the present study data were collected by means of a questionnaire administered partly before and partly after a genetic counselling session, to 35 mothers of African infants with DS. The results show that 83% of these mothers did not recognise any facial difference between their affected infant and other normal infants and 57% did not observe any other physical differences. After counselling, 40% of the sample still did not accept that their infant was different from other newborns. Only one mother was aware of infants with similar characteristics. These findings suggest that if mothers themselves cannot see the differences between their DS children and normal children, clinical diagnosis based on physical stigmata may be difficult. Furthermore, acceptance of the diagnosis may be retarded until delayed milestones can be observed in the affected infants.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03273.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

An analysis was performed on 40 families at risk for an unbalanced rearrangement in the fetus because one of the parents is a reciprocal translocation carrier. The overall risk at second trimester prenatal diagnosis was 14% (8/57). The individual risks for unbalanced offspring at second trimester prenatal diagnoses and at birth were estimated using empirical data by Stengel‐Rutkowski et al. (1988). The risks at birth ranged from 0%–21.6%. Most reciprocal translocations (22 or 55%) were at low risk. Without risk (7 or 17.5%), medium risk (6 or 15%) and high risk (5 or 12.5%) translocations were about equally represented and relatively infrequent. The analysis shows that the mode of ascertainment as well as the measurement of lengths of observed or probable imbalances cannot serve as a reliable risk predictor in individual counselling. In the translocations ascertained through spontaneous abortions the risk is frequently small or nonexistent, but remarkable exceptions to this rule are observed. Translocations discovered through unbalanced offspring were found to belong to different risk groups with the exception of the no risk group. Individual risk estimates have to be performed as a basis of genetic counselling before or during pregnancy so that parents with reciprocal translocations can make their choices regarding the available opti

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03274.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Wolcott‐Rallison syndrome is a rare autosomal recessive condition first described in 1972. It is characterised by diabetes mellitus which arises in early infancy and multiple epiphyseal dysplasia. We describe an affected girl who had recurrent episodes of hepatic failure for which no obvious cause was found. Post‐mortem examination revealed abnormal pancreatic histology and congenital abnormalities of the central nervous and cardio‐respiratory systems which have not been previously described in this condition. She also demonstrated a deletion at 15q 11–12 in 65% of he

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03275.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

“Jumping translocation” (jt) refers to a rare type of chromosome mosaic, in which the same portion of a (donor) chomosome is translocated to different (recipient) chromosome sites. It have mainly been observed in lymphocyte cultures of patients with hematologic malignancies. We report a phenotypically normal female carrying a mosaic of two cell lines with the Xq26‐qter segment translocated to the short arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts, only the X/21 translocation was detected. We speculate that recombination between homologous repetitive sequences on non‐homologous human acrocentrics may be the cause of such chromosomal rearran

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03276.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

In a 3‐month‐old boy with microcephaly, magnetic resonance imaging (MRI) revealed accumulation of bifrontal extracerebral fluid. Because of the typical MRI findings and the disappearance of these findings later on, he was diagnosed as a case of benign external hydrocephalus. Both his mother and maternal grandmother had microcephaly, without neurological or dysmorphic manifestations. The pedigree is most consistent with an autosomal dominantly inherited microcephaly. This seems to be the first report of benign external hydrocephalus found in a patient with an autosomal dominant microceph

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1996.tb03277.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY