Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Heterozygous copy-number and missense variants in CNTNAP2 and NRXN1 have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability. Methods 99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations in CNTNAP2 and NRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in either CNTNAP2 or NRXN1, the remaining allele was sequenced. Results By molecular karyotyping and mutational screening of CNTNAP2 and NRXN1 in a group of severely intellectually disabled patients we identified a heterozygous deletion in NRXN1 in one patient and heterozygous splice-site, frameshift and stop mutations in CNTNAP2 in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions within NRXN1 or CNTNAP2 we could identify a defect on the second allele. One deletion in NRXN1 and one deletion in CNTNAP2 occurred de novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation. Conclusions We report on patients with heterozygous defects in CNTNAP2 or NRXN1 associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.Peer Reviewe

Nine newly identified individuals refine the phenotype associated with MYT1L mutations

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Classification and Comparison of Modularity Concepts for Graph Transformation Systems

This paper presents a systematic approach for classifying and comparing modularity concepts that have been proposed for graph transformation systems. The approach is based on the following observation: Modules and module interconnections consist of basic specifications (forming, e.g., a module's body, import, or export interface), and relations between such specifications, like the implementation relation between export and body of a module. Hence, a natural approach for characterizing a module concept is to answer the following three questions: 1. What are the basic specifications? 2. Which relations between specifications are used? 3. How are specifications and relations combined to modules and interconnections? In this paper, these questions are considered in some detail for the following module concepts for graph transformation systems

Zur Wirkung von Metallkomponenten auf die acide Funktion von Reformingkatalysatoren

The influence of typical metal components of reforming catalysts on their acidic properties was investigated by means of i.r. spectroscopie methods using ammonia as probe molecule. It was shown that metal components in high oxidation states lead to an increased Lewis acidity and a small rise in the strength of Bronsied acid cenires especially in the case of the modification with rhenium. This effect is removed by the reduction process probably caused by a partial electron transfer from metal to the acidic centres