Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder

Currently there are no brief, self-administered instruments for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum. In this paper, we report on a new instrument to assess this: the Autism-Spectrum Quotient (AQ). Individuals score in the range 0-50. Four groups of subjects were assessed: Group 1: 58 adults with Asperger syndrome (AS) or high-functioning autism (HFA); Group 2: 174 randomly selected controls. Group 3: 840 students in Cambridge University; and Group 4: 16 winners of the UK Mathematics Olympiad. The adults with AS/HFA had a mean AQ score of 35.8 (SD = 6.5), significantly higher than Group 2 controls (M = 16.4, SD = 6.3). 80% of the adults with AS/HFA scored 32+, versus 2% of controls. Among the controls, men scored slightly but significantly higher than women. No women scored extremely highly (AQ score 34+) whereas 4% of men did so. Twice as many men (40%) as women (21%) scored at intermediate levels (AQ score 20+). Among the AS/HFA group, male and female scores did not differ significantly. The students in Cambridge University did not differ from the randomly selected control group, but scientists (including mathematicians) scored significantly higher than both humanities and social sciences students, confirming an earlier study that autistic conditions are associated with scientific skills. Within the sciences, mathematicians scored highest. This was replicated in Group 4, the Mathematics Olympiad winners scoring significantly higher than the male Cambridge humanities students. 6% of the student sample scored 32+ on the AQ. On interview, 11 out of 11 of these met three or more DSM-IV criteria for AS/HFA, and all were studying sciences/mathematics, and 7 of the 11 met threshold on these criteria. Test-retest and interrater reliability of the AQ was good. The AQ is thus a valuable instrument for rapidly quantifying where any given individual is situated on the continuum from autism to normality. Its potential for screening for autism spectrum conditions in adults of normal intelligence remains to be fully explored.

Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). To develop an equation to predict GFR from serum creatinine concentration and other factors. Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.

The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.