anxiety. This is the first evidence of young person self-report using both quantitative and qualitative data and indicates a range of reasons why young people may engage in RRB.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE , encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C . POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans . The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.

This is the third reported family with chromosome 19q13 rapid-onset dystonia-parkinsonism. Psychiatric morbidity appeared common in affected members of this family and may be part of the RDP phenotype.

Cholesterol is monitored in the non-pregnant adult population, where normal values are established. Although reported to be elevated in pregnancy, cholesterol is neither routinely measured nor treated. We aimed to investigate cholesterol levels throughout pregnancy and to establish reference values for cholesterol in healthy pregnant women. This was a cross-sectional analysis of serum cholesterol in healthy women with an uncomplicated singleton pregnancy. Pregnant women attending for antenatal care were recruited and cholesterol levels assayed at 12, 20, 28 and 36 weeks' gestation and on day 1-3 postpartum. A total of 222 women were recruited. The majority (95%) were white Irish, with a median age of 31 years (range 16-46). Median BMI was 25.9 kg/m2 (range 18-40) and 16% were smokers. Cholesterol levels were elevated in all trimesters of pregnancy, with median values from 1st trimester raised outside the non-pregnant adult range. High-density lipoprotein (HDL) levels ranged from 0.9 to 3.7 mmol/l and low-density lipoprotein (LDL) levels ranged from 1.3 to 6.1 mmol/l. Fasting, smoking and obesity did not have any significant effects on results. Total and LDL-cholesterol levels were raised throughout pregnancy. Levels were above non-pregnant adult ranges as early as the 1st trimester. The implications of this on fetus and mother are undetermined and deserve further investigation.

This should be the name the file is saved as when it is uploaded to our system, and should include the file extension. i.e.: Smith_SourceData_Fig1.xls, or Smith_ Unmodified_Gels_Fig1.pdf Data descriptioni.e.