Trisomy 10p with clinical features of facio-auriculo-vertebral spectrum: a case report

We report a male child born with complete absence of his external ear, hemifacial microsomia of the right side, high arched palate, a down-turned upper lip and slightly upslanting palpebral fissures. The features were suggestive of facio-auriculo-vertebral spectrum. Investigations showed a tandem duplication of the short arm of one chromosome 10 with apparent breakpoints at p14 and p15. This case extends the list of chromosomal abnormalities associated with the facio-auriculo-vertebral phenotype and also adds useful clinical information to possible trisomy 10p phenotypes.

Psychosocial impact of breast/ovarian (BRCA 1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort

This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes (BRCA 1/2) in the clinical context. In the year following predictive testing, 261 adults (59 male) from nine UK genetics centres participated; 9 I gene mutation carriers and 170 noncarriers. Self-report questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12 months following the genetic test result. Men were assessed for general mental health (by general health questionnaire (GHQ)) and women for general mental health, cancer-related worry, intrusive and avoidant thoughts, perception of risk and risk management behaviour. Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health. Female noncarriers benefited psychologically, with significant reductions in cancer-related worry following testing (P

Breast cancer genetics: Unsolved questions and open perspectives in an expanding clinical practice

Breast cancer is the most common cause of cancer death in the United Kingdom, with a lifetime risk of one in nine in women. Only 5-10% of all cancers is thought to be due to strongly penetrant inherited predisposing genes, such as BRCA1 and BRCA2. However, other less penetrant genes, including some autosomal recessive genes, are likely to be of etiological importance in other families. This review addresses the current knowledge of breast cancer susceptibility genes and explores the possibilities for future developments. Features of tumor pathology, prognosis, and the scope for targeted treatments in mutation carriers are discussed, and the management of known carriers and those at increased risk for developing breast cancer are evaluated. Genetic testing for cancer susceptibility may become widely available in the future, and has important ethical and management implications. (C) 2004 Wiley-Liss, Inc.

Mosaic monosomy 14: clinical features and recognizable facies

A 1-year-old child with clinical features of monosomy 14 is reported. She has dysmorphic facial features including ocular colobomata, dolichocephaly and microcephaly, retinal pigmentation, severe seizures, fair curly hair and tapering fingers. There was severe mental retardation. This is the first reported case of severe mosaic monosomy 14, with up to 30% mosaicism. A recognizable facial gestalt is present in children with 14q deletions or partial monosomy 14, as well as susceptibility to infection, feeding difficulties, seizures and retinal pigmentation. (C) 2004 Lippincott Williams Wilkins.

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: Attributes, cancer worry, and barriers to testing in a multicenter clinical cohort

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.

Strengthening Clinical Cancer Research in the United Kingdom

BACKGROUND: In 1999, 270,000 cases of cancer were registered in the United Kingdom, placing a large burden on the NHS. Cancer outcome data in 1999 suggested that UK survival rates were poorer than most other European countries. In the same year, a Department of Health review noted that clinical trials accrual was poor (

Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae

Tigecycline resistance has been attributed to ramA overexpression and subsequent acrA upregulation. The ramA locus, originally identified in Klebsiella pneumoniae, has homologues in Enterobacter and Salmonella spp. In this study, we identify in silico that the ramR binding site is also present in Citrobacter spp. and that Enterobacter, Citrobacter and Klebsiella spp. share key regulatory elements in the control of the romA–ramA locus. RACE (rapid amplification of cDNA ends) mapping indicated that there are two promoters from which romA–ramA expression can be regulated in K. pneumoniae. Correspondingly, electrophoretic binding studies clearly showed that purified RamA and RamR proteins bind to both of these promoters. Hence, there appear to be two RamR binding sites within the Klebsiella romA–ramA locus. Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation. We have identified changes within ramR in geographically distinct clinical isolates of K. pneumoniae. Intriguingly, levels of romA and ramA expression were not uniformly affected by changes within the ramR gene, thereby supporting the dual promoter finding. Furthermore, a subset of strains sustained no changes within the ramR gene but which still overexpressed the romA–ramA genes, strongly suggesting that a secondary regulator may control ramA expression.