Ten males with the fragile X (fra(X] syndrome were treated with folic acid (10 mg/day) for 4 months in a double-blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effort to study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co-ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5-year-old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder. Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acid-free medium but not in cells cultured in a medium with added antifolate (methotrexate). This shows a "contamination effect" of folate-free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early-replicating X when culturing with folic acid-free medium. A synergistic suppression effect of "external folate" and BrdU is the most likely explanation of this phenomenon.

Adolescent↗

PubMedDate not supplied

Fra(X) frequency on the active X-chromosome and phenotype in heterozygous carriers of the fra(X) form of mental retardation.

Female heterozygotes of the fra(X) form of mental retardation show variable degrees of mental impairment and phenotype expression of the disorder. This might be an effect of inactivation of the X-chromosome which carries the fra(X)(q). Prior replication studies in heterozygous carriers gave contradictory results with respect to possible genotype-phenotype correlation. In the interpretation of these studies it is important to understand the effect of BrdU on the fra(X)(q) expression. In a group of 13 hemizygous patients with fra(X)(q) and 7 heterozygous carriers we studied the effect of BrdU on fra(X) expression. In the heterozygous carriers the use of BrdU resulted in a significant suppression of the fra(X)(q), while in hemizygous patients no difference in fra(X)(q) frequency with or without BrdU could be observed. It can be concluded that BrdU suppresses the fra(X)(q) preferentially on the inactive X-chromosome. Thus the fra(X)(q) frequency on the active X-chromosome is of primary importance in phenotype correlation studies among heterozygous carriers. In our group of heterozygous carriers we observed a negative correlation between (IQ) phenotype and fra(X)(q) expression on the active X-chromosome. This suggests that the gene for the fra(X)(q) form of mental retardation is on the X-chromosome and undergoes inactivation.

Bromodeoxyuridine↗

PubMedDate not supplied

Prenatal diagnosis of a 46,XX/47,XX, + 12 mosaic.

A case of true mosaicism 46,XX/47,XX,+ 12 was diagnosed prenatally. The pregnancy was terminated in the 21st week of gestation and the aberrant cell line was rediscovered in cultured fetal tissue. However, a detailed examination of the fetus did not disclose any significant physical malformation.

Adult↗

PubMedDate not supplied

[Familial chromosome translocation (1;5;15) as a cause of partial trisomy 1p].

An unbalanced structural chromosome aberration was found in a 6-year-old girl. Mother and maternal grandmother were shown to be carriers of a complex balanced translocation involving chromosomes 1, 5 and 15 and are of normal phenotype. The unbalanced status in the proband was defined as a partial trisomy 1p21-1p31. Partial trisomies of this chromosomal segment have rarely been reported. Unexpectedly, the consequences on the child's phenotype are only minor. Main features are: facial dysmorphy, small stature and syndactyly of 4th and 5th toes; mental and statomotoric development are not grossly affected.

Abnormalities, Multiple↗

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R124C mutation of the betaIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1.

Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the betaIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the betaIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the betaIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course.

Adolescent↗

PubMedDate not supplied

Is intracytoplasmic sperm injection itself an indication to perform preimplantation genetic diagnosis (PGD)? About PGD, invasive prenatal diagnosis and genetic sonography.

Intracytoplasmic sperm injection (ICSI) provides the only sufficient treatment to overcome severe forms of male infertility. However, male infertility is linked to several genetic problems as an increased number of chromosomal aberrations, cystic fibrosis transmembrane conductance regulator gene mutations, Y-chromosome microdeletions, and androgen receptor mutations. Therefore, these couples are at a higher risk of transmitting genetic problems to their offspring compared to the general population. A proposed increased number of gonosomal aberrations in the offspring possibly results from the ICSI technique itself. This led in general to a worldwide agreement to counsel those couples to undergo invasive prenatal diagnosis in order to exclude chromosome abnormalities, especially gonosomal aberrations. In this paper the genetic risks of these couples and the possible implications of ICSI itself are discussed. Preimplantation genetic diagnosis may be considered a procedure of choice in these cases, but substantial ethical problems arise when such a screening is sought. An alternative procedure of prenatal diagnosis in these couples seems to be 'genetic sonography', i.e. high-resolution ultrasound with measurement of nuchal translucency at the end of the first trimester, and detailed fetal evaluation at 18-22 weeks of gestation.

Chromosome Aberrations↗

PubMedDate not supplied

[Chromosomal mosaicism after diagnostic chorionic villi biopsy. Subsequent study of the placenta].

Among 311 diagnostic chromosomal analyses after CVS eleven results (mostly chromosomal mosaicism) did not fit completely with the chromosomal sets found in the fetuses and newborns. In all cases chromosomal mosaicism was restricted to the placenta only. All children born after the diagnosis of a chromosomal mosaicism in the placenta were normal. In six cases the investigation of the placenta after termination of pregnancy or birth was possible. In all those cases the mosaicism could be found within the placenta, however, in some cases in a very low percentage. Although occurrence of chromosomal mosaicism in the placenta can hinder chromosomal diagnosis after CVS, the advantages of the method are not neutralized.

Abortion, Eugenic↗

PubMedDate not supplied

Studies in Down's syndrome. I. Genetic predisposition to become a carrier of the Au-SH antigen?

Explore the source record for details and available documents.

Adolescent↗