Failure to find DUP25 in patients with anxiety disorders, in control individuals, or in previously reported positive control cell lines

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

An investigation of FRAXA intermediate allele phenotype in a longitudinal sample

The FRAXA trinucleotide repeat at Xq27.3 gives rise to fragile X syndrome when fully expanded, and both premature ovarian failure (POF) and fragile X tremor and ataxia syndrome (FXTAS) when in the premutation range. Reports of phenotypic effects extending into the intermediate repeat range are inconsistent but some studies suggest that these smaller expansions predispose to special educational needs (SEN). This study utilises the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort to investigate cognitive and behavioural variables that might be associated with FRAXA intermediate alleles. The current study failed to find any strong evidence of association of FRAXA intermediate alleles with SEN, behavioural problems or cognitive difficulties. However, our findings illustrate some of the difficulties encountered in identifying individuals with SEN. The power to identify specific components of cognitive and behavioural difficulties was reduced due to elective drop-out, which is characteristic of longitudinal studies. Our findings demonstrate the non-random loss of participants from this cohort and highlight problems that may arise when such data are used in genetic association studie

Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study

Mortality and cancer incidence were assessed in a cohort of 1373 patients with numerical sex chromosome abnormalities diagnosed at three cytogenetics centres in Britain during 1959–90, and were compared with expectations from national rates. Four hundred patients with Turner's syndrome were followed, of whom 62 died, with a relative risk (RR) of death of 4.16 (95% confidence interval (CI) 3.22–5.39). Turner's syndrome patients had greatly raised risks of death from diseases of the nervous, cardiovascular, respiratory, digestive and genitourinary systems. One hundred and sixty three deaths occurred among 646 patients with Klinefelter's syndrome with a 47,XXY constitution, giving an RR of 1.63 (1.40–1.91). Mortality in these patients was significantly raised from diabetes and diseases of the cardiovascular, respiratory and digestive systems. There was also significantly increased mortality for patients with X polysomy (RR = 2.11 (1.43–3.02)) and Y polysomy (RR = 1.90 (1.20–2.85)), the former with significantly increased mortality from cardiovascular disease and the latter from respiratory disease. The only significantly raised risks of cancer incidence or mortality in the cohort were for lung cancer and breast cancer in patients with Klinefelter's syndrome with a 47,XXY constitution, and non-Hodgkin's lymphoma in men with more than three sex chromosomes

FRAXA and FRAXE: the results of a five year survey

We report the results of a five year survey of FRAXA and FRAXE mutations among boys aged 5 to 18 with special educational needs (SEN) related to learning disability. We tested their mothers using the X chromosome not transmitted to the son as a control chromosome, and the X chromosome inherited by the son to provide information on stability of transmission. We tested 3738 boys and 2968 mothers and found 20 FRAXA and one FRAXE full mutations among the boys and none among the mothers. This gives an estimated prevalence of full mutations in males of 1 in 5530 for FRAXA and 1 in 23?423 for FRAXE.We found an excess of intermediate and premutation alleles for both FRAXA and FRAXE. For FRAXA this was significant at the 0.001 level but the excess for FRAXE was significant only at the 0.03 level. We conclude that the excess of intermediate and premutation sized alleles for FRAXA may well be a contributing factor to the boys' mental impairment, while that for FRAXE may be a chance finding. We studied approximately 3000 transmissions from mother to son and found five instabilities of FRAXA in the common or intermediate range and three instabilities of FRAXE in the intermediate range. Thus instabilities in trinucleotide repeat size for FRAXA and FRAXE are rare, especially among alleles in the common size range. <br/