Turner Syndrome Research Today is a free monthly online journal that collates and summarizes the latest research about Turner Syndrome, including details on symptoms, causes, chromosomes, prognosis.

Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks.

Kerzendorfer C, Whibley A, Carpenter G, Outwin E, Chiang SC, Turner G, Schwartz C, El-Khamisy S, Raymond FL, O'Driscoll M

Human DNA Damage Response Disorders Group and.

CUL4A and B encode subunits of E3-ubiquitin ligases implicated in diverse processes including nucleotide excision repair, regulating gene expression and controlling DNA replication fork licensing. But, the functional distinction between CUL4A and CUL4B, if any, is unclear. Recently, mutations in CUL4B were identified in humans associated with mental retardation, relative macrocephaly, tremor and a peripheral neuropathy. Cells from these patients offer a unique system to help define at the molecular level the consequences of defective CUL4B specifically. We show that these patient-derived cells exhibit sensitivity to camptothecin (CPT), impaired CPT-induced topoisomerase I (Topo I) degradation and ubiquitination, thereby suggesting Topo I to be a novel Cul4-dependent substrate. Consistent with this, we also find that these cells exhibit increased levels of CPT-induced DNA breaks. Furthermore, over-expression of known CUL4-dependent substrates including Cdt1 and p21 appear to be a feature of these patient-derived cells. Collectively, our findings highlight the interplay between CUL4A and CUL4B and provide insight into the pathogenesis of CUL4B-deficiency in humans.

Published 29 January 2010 in Hum Mol Genet.
Full-text of this article is available online (may require subscription).

Articles on Turner Syndrome published 28 January 2010:

The effect of oxandrolone on body proportions and body composition in growth hormone-treated girls with Turner syndrome.   Clin Endocrinol (Oxf).

Summary Objective Untreated girls with Turner syndrome (TS) have short stature, relatively broad shoulders, a broad pelvis, short legs, a high fat mass, and low muscle mass. Our objective was to assess the effect of the weak androgen oxandrolone (Ox) on body proportions and composition in growth hormone (GH)-treated girls with TS. Design/Patients 133 patients were included in a randomised, placebo-controlled, double-blind study. Methods Patients were treated with GH (1.33mg/m(2)/day) from ... [Abstract] [Full-text]

Articles on Turner Syndrome published 27 January 2010:

Characteristics of the craniofacial complex in Turner syndrome.   Arch Oral Biol, 55(1): 81-8.

OBJECTIVE: To identify characteristics of the craniofacial complex in Turner syndrome (TS) patients from Croatian population, to investigate the interrelationship among craniofacial variables and to assess their correlation with age. DESIGN: Cephalometric analysis was carried out on lateral cephalograms of 36 TS patients, aged 10-33 years. Cephalograms of 72 age-matched healthy females with class I occlusion served as control. RESULTS: Logistic regression analysis sorted out two variables as ... [Abstract] [Full-text]

Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci.   Eur J Hum Genet.

This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell-Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The ... [Abstract] [Full-text]

Articles on Turner Syndrome published 26 January 2010:

Effect of sex hormone treatment on circulating adiponectin and subforms in Turner and Klinefelter syndrome.   Eur J Clin Invest.

Eur J Clin Invest 2010 Abstract Background Sex hormones have been shown to influence levels of adiponectin. Furthermore, testosterone has been shown to alter the subform distribution of adiponectin, whereas the effects of oestradiol are equivocal. We investigated the impact of sex hormone replacement therapy (HRT) on circulating adiponectin and its subforms, fasting lipids and measures of insulin sensitivity in Turner syndrome (TS) and Klinefelter syndrome (KS) respectively. Materials and ... [Abstract] [Full-text]

Articles on Turner Syndrome published 25 January 2010:

Observed and Predicted Growth Responses in Prepubertal Children with Growth Disorders: Guidance of Growth Hormone Treatment by Empirical Variables.   J Clin Endocrinol Metab.

Context: Information about the expected growth response of children to GH therapy is currently inadequate. Objectives: The aim of the study was to compare observed and expected growth in response to GH in prepubertal children and to propose how these parameters can be used to optimize GH therapy. Indices considered were observed growth, observed growth relative to reference data [height SD score (Ht SDS), change in (Delta) Ht SDS, height velocity (HV)], and observed growth relative to growth ... [Abstract] [Full-text]

Articles on Turner Syndrome published 20 January 2010:

High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome.   AIDS, 24(3): 427-35.

INTRODUCTION: This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time. METHODS: We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome ... [Abstract] [Full-text]

Articles on Turner Syndrome published 19 January 2010:

The effect of the weak androgen oxandrolone on psychological and behavioral characteristics in growth hormone-treated girls with Turner syndrome.   Horm Behav.

The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (GH) treated girls with Turner syndrome (TS), but may also give rise to virilizing side effects. To assess the effect of Ox, at a conventional and low dosage, on behavior, aggression, romantic and sexual interest, mood, and gender role in GH-treated girls with TS, a randomized, placebo-controlled, double-blind study was conducted. 133 patients were treated with GH (1.33 mg/m(2)/d) from baseline, combined with placebo ... [Abstract] [Full-text]

Articles on Turner Syndrome published 18 January 2010:

Laboratory guideline for Turner syndrome.   Genet Med, 12(1): 52-5.

Turner syndrome is a disorder that has distinct clinical features and has karyotypic aberrations with loss of critical regions of the X chromosome. Several clinical guidelines on the diagnosis and management of patients with Turner syndrome have been published, but there is relatively little on the laboratory aspects associated with this disorder. This disease-specific laboratory guideline provides laboratory guidance for the diagnosis/study of patients with Turner syndrome and its variants. ... [Abstract] [Full-text]

© 2005-2010 Turner Syndrome Research Today. All Rights Reserved.