The results argue against the heterozygote manifestation and suggest that the residual POR activity reflected by the R457H dosage constitutes the underlying factor for clinical variability in some features but not other features, probably due to the simplicity and complexity of POR-dependent metabolic pathways relevant to each phenotype.

These findings strongly suggest that this mutation leads to failure of processing of the IGF-IR proreceptor to mature IGF-IR and causes short stature and IUGR.

The Committee of the Japan Society for the Study of Obesity reported the new criteria for 'obesity disease' for Japanese adults in 2000. We defined the criteria for the diagnosis of obesity in children with medical problems, corresponding to the 'obesity disease' criteria in adults. Obesity in childhood was defined as follows: percentage of overweight (POW) and body fat exceeded the criteria. 'Obesity disease in childhood' was defined as obesity associated with health or medical problems, and with indications for medical intervention. Medical problems with indications for immediate intervention were grouped as A problems, which consisted of (i). hypertension; (ii). sleep apnea or hypoventilation; (iii). Type 2 diabetes mellitus or impaired glucose tolerance; and (iv). increased waist circumference or accumulation of visceral adipose tissue. Metabolic derangements or equivalent associated with obesity were grouped as B problems: (i). liver dysfunction; (ii). hyperinsulinemia; (iii). hypercholesterolemia; (iv). hypertriglyceridemia; (v). low serum high-density lipoprotein cholesterol; (vi). acanthosis nigricans, and (vii). hyperuricemia. Obese children over 5 years of age with following conditions were diagnosed as 'obesity disease in childhood': (i). any 'A problem', (ii) POW >or= 50% and any 'B problem', or (3) POW < 50% and more than one 'B problem' or equivalent. We decided to take physicosocial problems related to obesity into consideration as the criteria. The resultant criteria are proposed by the Committee for Research of Appropriate Body Build in Children*.

Antley-Bixler syndrome (ABS) is characterized by skeletal defects including craniosynostosis and radiohumeral synostosis. Although mutations in the FGFR2 gene have been found in some patients called ABS, genetic heterogeneity of this syndrome has been proposed. We have previously reported three ABS patients with unique abnormalities in steroidogenesis (apparent decreased activity of 17alpha-hydroxylase, 17,20-lyase, and 21-hydroxylase). Decreased activity of lanosterol 14alpha-demethylase has also been described in an ABS patient. Since all these enzymes require cytochrome P450 oxidoreductase (encoded by POR) as an electron donor, we studied POR in two unrelated ABS patients with abnormal steroidogenesis. Direct sequencing of POR revealed that both patients had compound heterozygous mutations (1329insC and R454H in a male patient, 1698insC and R454H in a female patient). The two insertional mutations were assumed to generate truncated and unstable mRNAs. The R454H mutation was assumed to be deleterious because the R454 resides in the FAD-binding domain and is highly conserved among diverse species. Our results demonstrate that mutations in POR cause the ABS phenotype with autosomal recessive inheritance and with characteristic abnormalities in steroidogenesis.

This study demonstrated the characteristic association of HLA-class II and class I genes with Type 1A diabetes among Japanese children. A TDT did not reveal the genomic imprinting of HLA-class II and class I genes in Type 1A diabetes.

A missense mutation (R431L) leads to the inhibition of cell proliferation, attenuation of IGF signalling and decrease in internalization of IGF-IR. The results of this study suggest a novel link between a mutation at the IGF-IR L2 domain and intrauterine and postnatal growth retardation.

This study provides novel mechanisms leading to gain of function of CYP19A1. Furthermore, it appears that clinical severity of AEXS is primarily determined by the tissue expression pattern of relevant genes and by the structural property of promoter-associated exons of chimeric mRNA.

Using multivariate regression analysis, we examined risk factors for fatality and neurological sequelae after status epilepticus (SE) in children. Possible risk factors included sex, age at onset, the cause of SE, pyrexia, asthmatic attack during SE, past history of seizure, predisposing neurological abnormality, seizure duration, type of seizure, and medication with theophylline. Consecutive patients with SE, aged 1 month to 18 years, who were referred to Tottori University Hospital from 1984 to 2002 were reviewed. Of the 234 patients enrolled, 45 patients (19.2 %) showed poor outcomes, namely early death in 9 and neurological sequela in 36. Acute neurological insult and progressive neurological disease as the cause of SE were very significantly related to poor outcome (OR = 33.68, p = 0.000). We excluded 21 patients with the etiology of acute neurological insult and progressive neurological disease and then reanalyzed risk factors in the remaining 213 patients. Twenty-nine patients (13.6 %) showed poor outcome, namely early death in 6 and neurological sequela in 23. Seizure duration of more than 2 hours (OR = 12.73, p = 0.000) and moderate to severe asthmatic attack (OR = 31.61, p = 0.010) were associated with poor outcome. These results indicate that long-lasting seizure activity and asthmatic attack can exacerbate SE-associated brain injury.