Mutations in the ribosomal protein gene RPL10 suggest a novel modulating disease mechanism for autism.

Autism has a strong genetic background with a higher frequency of affected males suggesting involvement of X-linked genes and possibly also other factors causing the unbalanced sex ratio in the etiology of the disorder. We have identified two missense mutations in the ribosomal protein gene RPL10 located in Xq28 in two independent families with autism. We have obtained evidence that the amino-acid substitutions L206M and H213Q at the C-terminal end of RPL10 confer hypomorphism with respect to the regulation of the translation process while keeping the basic translation functions intact. This suggests the contribution of a novel, possibly modulating aberrant cellular function operative in autism. Previously, we detected high expression of RPL10 by RNA in situ hybridization in mouse hippocampus, a constituent of the brain limbic system known to be afflicted in autism. Based on these findings, we present a model for autistic disorder where a change in translational function is suggested to impact on those cognitive functions that are mediated through the limbic system.

Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients.

A genetic etiology in autism is now strongly supported by family and twin studies. A 3:1 ratio of affected males to females suggests the involvement of at least one X-linked locus in the disease. Several reports have indicated an association of the fragile X chromosomal anomaly at Xq27.3 (FRAXA) with autism, whereas others have not supported this finding. We have so far collected blood from 105 simplex and 18 multiplex families and have assessed 141 patients by using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Scale, and psychometric tests. All four ADI-R algorithm criteria were met by 131 patients (93%), whereas 10 patients (7%) showed a broader phenotype of autism. Southern blot analysis was performed with three different enzymes, and filters were hybridized to an FMR-1-specific probe to detect amplification of the CCG repeat at FRAXA, to the complete FMR-1 cDNA probe, and to additional probes from the neighborhood of the gene. No significant changes were found in 139 patients (99%) from 122 families, other than the normal variations in the population. In the case of one multiplex family with three children showing no dysmorphic features of the fragile X syndrome (one male meeting 3 out of 4 ADI-algorithm criteria, one normal male with slight learning disability but negative ADI-R testing, and one fully autistic female), the FRAXA full-mutation-specific CCG-repeat expansion in the genotype was not correlated with the autism phenotype. Further analysis revealed a mosaic pattern of methylation at the FMR-1 gene locus in the two sons of the family, indicating at least a partly functional gene. Therefore, we conclude that the association of autism with fragile X at Xq27.3 is non-existent and exclude this location as a candidate gene region for autism.

The standardized diagnosis of autism, Autism Diagnostic Interview-Revised: interrater reliability of the German form of the interview.

The feasibility and reliability of the German form of the revised parental interview to diagnose autism (Autism Diagnostic Interview-Revised, ADI-R) was investigated in this study. Brief examples of the description of formerly and currently used diagnostic guidelines are given and the outline of the interview algorithm which establishes thresholds for inclusion criteria. An excellent-to-good reliability could be demonstrated for the main symptoms according to the classification rules of the ICD-10 and DSM-IV for a sample of autistic subjects at different ages and intellectual levels. The results approve the use of this interview for research and clinical purposes.

The influence of the regular use of a soap or an acidic syndet bar on pre-acne.

The role of regular skin cleansing with soap or syndet in pre-acne is ill-defined. The intention of this study was to assess the relative value of an acidic syndet bar and a conventional soap bar in the prevention of acne lesions in acne-prone patients. In a randomized, open, comparative trial the three months' application of either an acidic syndet bar or a conventional soap to facial skin for 1 min each in the morning and in the evening was compared in 120 adolescents and young adults with inflammatory acne grade I or II according to the Plewig and Kligman classification. It was a confirmatory trial with the number of inflammatory lesions being the prime parameter of concern. In addition, non-inflammatory acne lesions were analyzed as were parameters of safety such as itching, redness and scaling. While the number of inflammatory acne lesions, i.e., papulopustules, did not differ in the two trial groups composed of 57 evaluable cases each, this was the case from 4 weeks of application onward: in the group using soap the mean number of inflammatory lesions increased from 14.6 (+/- 5.3) to 15.3 (+/- 6.0), while it decreased in the other group from 13.4 (+/- 5.2) to 10.4 (+/- 5.8) (p < 0.0001). Symptoms or signs of irritation were seen in 40.4% of individuals belonging to the former and 1.8% belonging to the latter group. The number of papulopustules characteristic of inflammatory acne thus is clearly lower when a syndet bar of the acidic type is regularly used for cleansing the face as compared to a (necessarily alkaline) soap.(ABSTRACT TRUNCATED AT 250 WORDS)