The underlying cause of mental retardation remains unknown in up to 80% of patients. As chromosomal aberrations are the most common known cause of mental retardation, several new methods based on FISH, PCR, and array techniques have been developed over recent years to increase detection rate of subtle aneusomies initially of the gene rich subtelomeric regions, but nowadays also genome wide. As the reported detection rates vary widely between different reports and in order to compare the diagnostic yield of various investigations, we analyzed the diagnostic yield of conventional karyotyping, subtelomeric screening, molecular karyotyping, X‐inactivation studies, and dysmorphological evaluation with targeted laboratory testing in unselected patients referred for developmental delay or mental retardation to our cytogenetic laboratory (n = 600) and to our genetic clinic (n = 570). In the cytogenetic group, 15% of patients showed a disease‐related aberration, while various targeted analyses after dysmorphological investigation led to a diagnosis in about 20% in the genetic clinic group. When adding the patients with a cytogenetic aberration to the patient group seen in genetic clinic, an etiological diagnosis was established in about 40% of the combined study group. A conventional cytogenetic diagnosis was present in 16% of combined patients and a microdeletion syndrome was diagnosed in 5.3%, while subtelomeric screening revealed only 1.3% of causes. Molecular karyotyping with a 10 K SNP array in addition revealed 5% of underlying causes, but 29% of all diagnoses would have been detectable by molecular karyotyping. In those patients without a clear diagnosis, 5.6% of mothers of affected boys showed significant (>95%) skewing of X‐inactivation suggesting X‐linked mental retardation. The most common diagnoses with a frequency of more than 0.5% were Down syndrome (9.2%), common microdeletion 22q11.2 (2.4%), Williams–Beuren syndrome (1.3%), Fragile‐X syndrome (1.2%), Cohen syndrome (0.7%), and monosomy 1p36.3 (0.6%). From our data, we suggest the following diagnostic procedure in patients with unexplained developmental delay or mental retardation: (1) Clinical/dysmorphological investigation with respective targeted analyses; (2) In the remaining patients without an etiological diagnosis, we suggest conventional karyotyping, X‐inactivation screening in mothers of boys, and molecular karyotyping, if available. If molecular karyotyping is not available, subtelomeric screening should be performed. © 2006 Wiley‐Liss, Inc.

Intellectual disability (ID) is a clinically and genetically heterogeneous common condition that remains etiologically unresolved in the majority of cases. Although several hundred diseased genes have been identified in X-linked, autosomal-recessive, or syndromic types of ID, the establishment of an etiological basis remains a difficult task in unspecific, sporadic cases. Just recently, de novo mutations in SYNGAP1, STXBP1, MEF2C, and GRIN2B were reported as relatively common causes of ID in such individuals. On the basis of a patient with severe ID and a 2.5 Mb microdeletion including ARID1B in chromosomal region 6q25, we performed mutational analysis in 887 unselected patients with unexplained ID. In this cohort, we found eight (0.9%) additional de novo nonsense or frameshift mutations predicted to cause haploinsufficiency. Our findings indicate that haploinsufficiency of ARID1B, a member of the SWI/SNF-A chromatin-remodeling complex, is a common cause of ID, and they add to the growing evidence that chromatin-remodeling defects are an important contributor to neurodevelopmental disorders.

BackgroundPatients with schizophrenia have lower longevity than the general population as a consequence of a combination of risk factors connected to the disease, lifestyle and the use of medications, which are related to weight gain.MethodsA multicentric, randomized, controlled-trial was conducted to test the efficacy of a 12-week group Lifestyle Wellness Program (LWP). The program consists of a one-hour weekly session to discuss topics like dietary choices, lifestyle, physical activity and self-esteem with patients and their relatives. Patients were randomized into two groups: standard care (SC) and standard care plus intervention (LWP). Primary outcome was defined as the weight and body mass index (BMI).Results160 patients participated in the study (81 in the intervention group and 79 in the SC group). On an intent to treat analysis, after three months the patients in the intervention group presented a decrease of 0.48 kg (CI 95% -0.65 to 1.13) while the standard care group showed an increase of 0.48 kg (CI 95% 0.13 to 0.83; p=0.055). At six-month follow-up, there was a significant weight decrease of −1.15 kg, (CI 95% -2.11 to 0.19) in the intervention group compared to a weight increase in the standard care group (+0.5 kg, CI 95% -0.42–1.42, p=0.017).ConclusionIn conclusion, this was a multicentric randomized clinical trial with a lifestyle intervention for individuals with schizophrenia, where the intervention group maintained weight and presented a tendency to decrease weight after 6 months. It is reasonable to suppose that lifestyle interventions may be important long-term strategies to avoid the tendency of these individuals to increase weight.Clinicaltrials.gov identifierNCT01368406

Objective: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). Method: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls.Results: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was #45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) 31X7^6X7 kgam 2 Y P 0X0058 and an increased prevalence of obesity (81%, P 0X005 with respect to heterozygous subjects 27X95 X0 kgam 2 ; 46%) or homozygous subjects for the t-allele 27X7^5X0 kgam 2 ; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% con®dence interval (CI), 1.64±14.76; P 0X0056. Conclusion: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.