Genotyping of fanconi anemia patients by whole exome sequencing: advantages and challenges

Fanconi anemia (FA) is a rare genomic instability syndrome. Disease-causing are biallelic mutations in any one of at least 15 genes encoding members of the FA/BRCA pathway of DNA-interstrand crosslink repair. Patients are diagnosed based upon phenotypical manifestationsand the diagnosis of FA is confirmed by the hypersensitivity of cells to DNA interstrand crosslinking agents. Customary molecular diagnostics has become increasingly cumbersome, time-consuming and expensive the more FA genes have been identified. We performed Whole Exome Sequencing (WES) in four FA patients in order to investigate the potential of this method for FA genotyping. In search of an optimal WES methodology we explored different enrichment and sequencing techniques. In each case we were able to identify the pathogenic mutations so that WES provided both, complementation group assignment and mutation detection in a single approach. The mutations included homozygous and heterozygous single base pair substitutions and a two-base-pair duplication in FANCJ, -D1, or - D2. Different WES strategies had no critical influence on the individual outcome. However, database errors and in particular pseudogenes impose obstacles that may prevent correct data perception and interpretation, and thus cause pitfalls. With these difficulties in mind, our results show that WES is a valuable tool for the molecular diagnosis of FA and a sufficiently safe technique, capable of engaging increasingly in competition with classical genetic approaches

Development and Psychometric Properties of a New Questionnaire to Assess Mental Health and Concerning Behaviors in Children and Young People with Autism Spectrum Disorder (ASD):The Assessment of Concerning Behavior (ACB) Scale

Although 70% of autistic children and young people meet criteria for co-occurring psychiatric conditions, there are few screening measures specifically for autistic individuals. We describe the development and validation of the Assessment of Concerning Behavior (ACB), an instrument co-developed with the autistic community to assess mental health and problematic/risky behaviors. Items include descriptions to facilitate symptom recognition by autistic people, and carers/professionals. The ACB was completed by 255 parents, 149 autistic children and young people and 30 teachers. Internal consistency, stability and validity was assessed. The ACB parent-version fit a two-factor model (internalizing and externalizing problems) and showed adequate test–retest reliability, internal consistency and construct validity. The ACB is a promising new measure for research and clinical use in autism