Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase gamma (POLG1) have recently been described in patients with diverse clinical presentations, revealing a complex relationship between genotype and phenotype in patients and their families. POLG1 was sequenced in patients from different European diagnostic and research centres to define the phenotypic spectrum and advance understanding of the recurrence risks. Mutations were identified in 38 cases, with the majority being sporadic compound heterozygotes. Eighty-nine DNA sequence changes were identified, including 2 predicted to alter a splice site, 1 predicted to cause a premature stop codon and 13 predicted to cause novel amino acid substitutions. The majority of children had a mutation in the linker region, often 1399G-->A (A467T), and a mutation affecting the polymerase domain. Others had mutations throughout the gene, and 11 had 3 or more substitutions. The clinical presentation ranged from the neonatal period to late adult life, with an overlapping phenotypic spectrum from severe encephalopathy and liver failure to late-onset external ophthalmoplegia, ataxia, myopathy and isolated muscle pain or epilepsy. There was a strong gender bias in children, with evidence of an environmental interaction with sodium valproate. POLG1 mutations cause an overlapping clinical spectrum of disease with both dominant and recessive modes of inheritance. 1399G-->A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling.

In childhood, the most common site of fracture is the distal forearm. To determine whether young girls with these fractures have low bone density more commonly than fracture-free controls, we measured bone density at the radius, spine, hip, and whole body and total body bone mineral content, lean tissue mass, and fat mass by dualenergy X-ray absorptiometry in 100 Caucasian girls aged 3-15 years with recent distal forearm fractures and 100 age-and gender-matched controls. Bone density (age-adjusted ratios of all cases:controls with 95% confidence intervals) was lower in cases at the ultradistal radius 0.

OBJECTIVES: To determine whether girls and boys categorized from body mass index (BMI) values as overweight or obese for their age have lower bone mineral content (BMC) or lower bone area in relation to total body weight than children of normal adiposity. DESIGN: Cross-sectional study in a university bone research unit. SUBJECTS: Two hundred girls and 136 boys aged 3 ± 19 y recruited from the general population by advertisement. MEASUREMENTS: Total body BMC (g) and bone area (cm 2 ) measured by dual energy X-ray absorptiometry (DXA) in relation to body weight (kg), lean tissue mass (kg) and fat mass (kg) in boys and girls of three different BMI percentile groupings: normal weight (BMI`85th percentile); overweight (85 to 94th BMI percentile); obese ( 95th BMI percentile). RESULTS: Obese children had higher BMC, bone area, and fat mass for chronological age than those of normal body weight (P`0.001). In spite of this the observed values for age-adjusted total body BMC and bone area relative to body weight were each lower than predicted values, in both overweight and obese children (2.5 ± 10.1% less, P`0.05) than in children of lower adiposity. CONCLUSION: In overweight and obese boys and girls there is a mismatch between body weight and bone development during growth: their bone mass and bone area are low for their body weight.

Receiver operating characteristic (ROC) curves were constructed to assess the value of body mass index (BMI) as a screening measure for total adiposity and to examine waist-to-hip ratio (WHR) and waist circumference as measures of central fat distribution. Body fat reference measurements were determined by dual-energy X-ray absorptiometry (DXA). The study population comprised 96 healthy white women aged 16-80 y. A positive reference test was defined as a result at or above the 75th percentile for our study population for all DXA measurements. Sensitivity and specificity were calculated at several percentile cutoffs for BMI, WHR, and waist girth. The areas under the ROC curves were calculated to compare the relative ability of each anthropometric technique to correctly classify subjects according to the reference measurement for that technique. BMI (our 75th percentile = 27.3) performed well as a screening measure of total adiposity, correctly identifying 83% of subjects with a high body fat mass while misclassifying only eight subjects [four false-negatives (subjects with high fat mass who were in the low BMI category) and four false-positives (subjects with a low fat mass who were in the high BMI category)]. The screening performance of WHR (our 75th percentile = 0.81) was lower, accurately categorizing 58% of subjects while misclassifying 28 subjects. By contrast, waist circumference (our 75th percentile = 86.9 cm) was significantly better than WHR at screening for regional fat distribution, accurately classifying 83% of subjects and misclassifying eight subjects (P < 0.05). We conclude that BMI and waist circumference provide simple yet sensitive methods for the estimation of total and central adiposity in groups of adult women.

Diabetologia (2005) 48:8-16Unfortunately there was a mistake in the Abstract of this paper. The third sentence in the 'Results' section should have read:When compared with the HC diet, the HF and HP diets were shown to produce significantly (p<0.01) greater reductions in several parameters, including weight loss (HF −2.8 kg, HP −2.7 kg), waist circumference (HF −3.5 cm, HP −2.7 cm) and triglycerides (HF −0.30 mmol/l, HP −0.22 mmol/l).The online version of the original article can be found at http://dx.