DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P ¼ 0.02, Odds ratio ¼ 4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an An increased frequency of several psychotic disorders, such as children-onset schizophrenia, 1 schizophrenia, 2 and bipolar disorder, 3 has been observed in patients with the 22q11 deletion syndromes (22q11DS), 4 which include the DiGeorge syndrome (MIM 188400) and the velo-cardio-facial syndrome (MIM 192430). This has led to the hypothesis that sequence variations of one or several genes located within the 3 Mb region commonly deleted in most of the 22q11DS patients 5 might confer susceptibility for psychoses in the general population. In a previous study, we had identified in two schizophrenic relatives (diagnosed according to DSM III criteria) a 350 kb heterozygous deletion within the DiGeorge critical region (DGCR) removing entirely the proline dehydrogenase (PRODH) gene. This deletion was associated in patients with moderate hyperprolinemia. In addition, two heterozygous PRODH missense mutations (L441P and L289M) were detected in three of 63 schizophrenic patients but not in 68 controls, and these mutations were also associated with moderate hyperprolinemia. 6 Interestingly, we subsequently found the same PRODH deletion and the L441P substitution at the homozygous state in children suffering from a severe form of type I hyperprolinemia, a condition characterized by high plasma proline levels, seizures and mental retardation. 7 T...

Our results suggest that the presentation of hypothyroidism is altered in the elderly in comparison with young patients in that there are (1) fewer signs or symptoms and (2) diminished frequency of some classical signs. Our results underline the importance of TSH measurement in the elderly.

Our study confirms that factor V Leiden mutation increases the risk for thrombotic events but is not more frequent in patients with inflammatory bowel disease. Our results do not support the role of other thrombotic risk factors.