摘要:

All the cases of Friedreich's ataxia (FA) diagnosed between 1945 through 1984 among residents of a defined area of northwestern Italy were ascertained (N = 59). Cases were diagnosed according to the criteria of the “Quebec Cooperative Study on Friedreich's Ataxia (QCSFA)” with minor modifications. We identified 39 families with 47 probands and 12 secondary cases. Therefore ascertainment probability was 80%. Male to female ratio was 1:1. Pedigrees were compatible with autosomal recessive inheritance. Segregation ratio was 0.28 with both Weinberg's method and the “singles” method (under incomplete ascertainment). Point prevalence ratio was 1.2/100 000 population. Birth incidence rate was 1/36 000 live births. Gene frequency was estimated to be 1/191. The ratio of first‐cousin marriages observed among parents of FA patients (3%) was lower than expected from Dahlberg's formula (8%). This finding is not compatible with the hypothesis of genetic heterogenei

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03566.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Four sibs with varying degrees of caudal dysgenesis are described. Case 1 showed aberrant umbilical cord vasculature with a single umbilical artery near the placental insertion. Cases 2 and 3 showed full sirenomelia, one with a complex congenital heart defect. Case 4 had an imperforate anus and an excessively long umbilical cord. The father's half‐sib had an imperforate anus, rectovaginal fistula and genitourinary anomalies. A dominant gene with reduced penetrance is likel

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03567.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Five Bedouin sibs are described with Meckel‐Gruber syndrome (MGS), an autosomal recessive disorder with multiple abnormalities. Each affected sib manifested only two of the three cardinal signs of MGS: occipital encephalocele and polycystic kidneys, lacking polydactyly. The phenotypic variability of the MGS pleiotropic gene is briefly discusse

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03568.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A study of very early onset Huntington's disease (VEOHD) has shown that at least 38% of gene‐carrying sibs also develop symptoms before the age of 10, thus improving the genetic risk for those sibs who remain healthy. The prevalence of VEOHD among sibs shows that mutation during spermatogenesis is most unlikely to account for these uncommon cases. The data suggest that two mechanisms contribute to VEOHD: modification by many genes (individually of small effect), and an epigenetic mechanism occurring when transmission is through a series of male

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03569.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

With the aim of determining the usefulness of RFLP analysis in carrier detection and prenatal diagnosis, we studied all available members including 40 patients, 30 obligate carriers and 39 women at risk belonging to 19 out of a total of 20 Finnish hemophilia B families. The allele frequencies of the three intragenic polymorphisms studied (TaqI, XmnI and DdeI) did not differ significantly from those reported in other Caucasian populations. A considerable degree of linkage disequilibrium between the three polymorphisms was observed. Carriership evaluated in 39 females at risk led to exclusion in 14 while carriership was established in 5. The proportion of women who by pedigree analysis had a carriership risk between 10% and 90% could be reduced from 97% to 51% by RFLP analysis. Prenatal diagnosis using an intragenic polymorphism could potentially be offered to 69% of hemophilia carriers. DNAs from 19 unrelated patients were screened for mutations using a full‐length cDNA probe, but no abnormal hybridization patterns were observed. Our results indicate that RFLP segregation analysis provides a useful method of carrier detection and prenatal diagnosis in hemophilia

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03570.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Nine cases of congenital cardiovascular malformations (CCVM) with associated unbalanced structural chromosomal abnormalities were ascertained in a population‐based study of heart defects, constituting 0.4% of the 2,103 cases of CCVM in the Baltimore‐Washington Infant Study (BWIS). This represents a four‐fold increase over the general population rate. In an effort to determine possible phenotype/karyotype correlations, the literature was searched for cases with similar karyotypic abnormalities. This comparison of 223 literature cases of karyotypic abnormalities with nine similar cases ascertained by heart malformation has provided the opportunity to review cardiac defects reported in cases of structural abnormalities of chromosomes 1, 3, 7, 8, 9, 10, 11, 15, and 18. The most common cardiac malformation present in the chromosomal cases was ventricular septal defect (VSD) (39%); similarly VSD is the most common CCVM among children with heart defects, although it is the primary defect in only 20% of the BWIS cases. Among all heart defects in the BWIS, atrial septal defect (ASD) represents 5.5% of all cases, but in cases of 8p duplication, ASD is present in 41%. In addition, 40% of cases of 9p duplication had an ASD. Similarly, 35% of cases of 11q duplication had an ASD. While the suggestion of specific karyotype/phenotype associations is premature, information on additional cases might clarify the possibility that genetic determinants related to septum formation may reside on chromosome 8, 9, and/or 11. The variety of chromosomal abnormalities in cases with ventricular septal defect indicates one type of genetic heterogeneity that may be involved in this very common heart d

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03571.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Seventy‐five selective terminations, based on abnormal laboratory findings at first‐trimester CVS, were performed in 1581 consecutive pregnancies. In all cases a (semi‐) direct method of cytogenetic analysis was used. The 75 abortions were analysed in number of ways. Confirmatory studies showed that three cases had to be considered as false‐positive findings, and in one other case the results were inconclusive. Based on literature data, it was estimated that 41 of the 75 pregnancies would have resulted in seriously handicapped children, surviving beyond the age of 1 year, if no termination of pregnancy had taken place. Negative side‐effects of the procedure include: spontaneous abortion of chromosomally normal fetuses due to the CVS procedure itself and the need for a number of secondary amniocenteses (5.1%). The advantage of DNA diagnosis in X‐linked diseases is illustrated by comparing the CVS results with a previously published amniocen

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03572.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Glucocerebrosidase activity in extracts of leukocytes, Epstein‐Barr virus transformed lymphocytes and fibroblasts from Portuguese Type 1 Gaucher disease patients was studied. The residual glucocerebrosidase activity in all extracts from patients was less than 25% if measured in the presence of bile salt taurocholate. However, if measured in the absence of bile salt the residual enzyme activity in extracts from patients was cell type specific: it was severely reduced in the case of fibroblasts, mildly reduced in the case of lymphoblasts and not significantly reduced in the case of leukocytes. The glucocerebrosidase activity in extracts from all control cell types was stimulated by taurocholate. In the patients the enzyme activity in fibroblasts extracts was also stimulated but that in lymphoblasts and leukocytes was inhibited by the bile salt. The differences in glucocerebrosidase activity (in the absence of taurocholate) in extracts from different cell types from Gaucher disease patients are attributable to differences in the proportion of glucocerebrosidase present as a monomer with low activity (form I) and as a highly active aggregate (form II) that may also contain sphingolipid activator protein 2 (SAP‐2). In extracts from leukocytes and lymphocytes from Type 1 Gaucher disease patients, but not in those from fibroblasts, a relatively high proportion of enzyme is present in aggregated form with near normal specific activ

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03573.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A patient who presented with most features of lacrimo‐auriculo‐dento‐digital (LADD) syndrome, an autosomal dominant trait, is described. There was no deafness, and anomalies of the external ear and the upper limbs were discrete. Renal anomalies, consisting of progressive caliectasis with stone formation, were revealed by macroscopic hematuria. There were also skeletal anomalies of both feet, a feature not previously described. Renal and distal limb anomalies are probably features of LADD syn

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03574.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We describe a 10‐year‐old girl with features of a frontonasal dysplasia and a right‐sided Poland anomaly. As there has been one previous case report of pectoral muscle hypoplasia in association with craniofrontonasal dysplasia, the relationship between these two conditions is disc

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1990.tb03575.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY