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Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of various forms of interstitial duplications involving human chromosome 15q24-q26 (named "DUP25") in a Spanish population. DUP25 was observed in 68 of 70 (97%) patients assigned the diagnosis panic disorder/agoraphobia. DUP25 was also found in 14 of 189 (7%) control individuals. In the present study, we replicated the experimental conditions described by Gratacòs and colleagues in which fluorescence in situ hybridization was used to examine metaphase chromosomes of patients with panic disorder/social phobia and of control individuals from a southern region of the United Kingdom, the primary aim being to determine the prevalence of this chromosomal rearrangement in a geographically and ethnically distinct population. DUP25 was not observed in any of our 16 patients or 40 control samples or in three previously reported DUP25-positive control (Centre d'Etude du Polymorphisme Humain) cell lines, indicating a highly significant difference in the frequency of DUP25 between the study by Gratacòs and colleagues and the present investigation. [ABSTRACT FROM AUTHOR]

Presents a study which examined whether variation at methylenetetrahydrofolate (MTHFR) reductase or methionine synthase reductase (MTRR) might be associated with human trisomies. Analysis on maternal polymorphisms at MTHFR and MTRR in cases of sex-chromosome trisomy; Effect of polymorphisms in the folate pathway in human meiotic nondisfunction.

We have used polymorphisms within the Xp/Yp pseudoautosomal region (PAR 1) to determine the frequency and location of recombination in 80 paternally derived 47, XXY males. Of 64 informative results, there were 10 single cross-overs, one double cross-over and 53 without a cross-over. Therefore 2/3 of 47, XXY males of paternal origin result from meiosis in which the X and Y chromosomes fail to recombine. This failure was not associated with the presence of an increase in recombination in the smaller Xq/Yq pseudoautosomal region (PAR 2) or with the presence of microdeletions within PAR 1. [ABSTRACT FROM AUTHOR]

FRAXE full mutations are rare and appear to be associated with mild mental retardation. As part of a screening survey of boys with learning difficulties to determine the frequency of full and premutations, we have collected data on the frequency of instability at FRAXE for about 4000 transmissions and the haplotype for over 7000 chromosomes. The distribution of FRAXE repeats was similar to other English populations but differed from two North American Caucasian series. Observed instability at FRAXE was rare but increased with increasing repeat number, and there were no expansions into the full mutation range, except in pedigrees ascertained through a full mutation. Haplotype analysis suggested division into five groups with each group having a characteristic distribution of FRAXE repeats. Fourteen of the 15 full mutations occurred on a single haplotype and this haplotype also had a significant excess of intermediate-sized alleles, suggesting that full mutations originate from large normal alleles. However, a related haplotype also had a significant excess of intermediates but we observed no full mutations on this haplotype, suggesting either loss or gain of stability determinants on it. We suggest that whilst triplet repeat size is a significant predisposing factor for expansion at FRAXE other genetic determinants are also likely to be important. [ABSTRACT FROM AUTHOR]

We studied four families each with three trisomy 21 conceptions. In two of the families the trisomy 21 conceptions all occurred when the mothers were under 35 years of age and in the other two families they all occurred when the mothers were over 35 years of age. Cytogenetic studies showed low level mosaic trisomy 21 in the two younger mothers, but not in the two older. In the three families tested using molecular techniques the results were consistent with the additional chromosome 21 in the trisomic conceptuses being maternally derived. Novel alleles were detected in the trisomic offspring of one of the younger mothers, demonstrating that the mother had been conceived as a trisomy with three different chromosomes 21. Therefore the multiple trisomy 21 pregnancies in the two younger mothers resulted from maternal trisomy 21 mosaicism, but may have been due to chance in the older mothers. [ABSTRACT FROM AUTHOR]

Premutations of the fragile-X (FRAXA) gene were thought to have no clinical effects until recent reports of an increased incidence of premature ovarian failure in females and a late-onset neurological disorder in males. These patients were identified from families including typical fragile-X males with a full mutation. By analysing a cohort of patients with neurodegenerative disorders referred for genetic analysis of spinocerebellar ataxia genes, we have found that 3 of 59 males carry the premutation. Our patients extend the phenotype associated with the FRAXA premutation and indicate that it may account for a proportion of undiagnosed neurodegenerative disorders. [ABSTRACT FROM AUTHOR]