Novel mutations in the PEX12 gene of patients with a peroxisome biogenesis disorder

The peroxisome biogenesis disorders (PBDs) form a genetically and clinically heterogeneous group of disorders due to defects in at least 11 distinct genes. The prototype of this group of disorders is Zellweger syndrome (ZS), with neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) as milder variants. Liver disease, variable neurodevelopmental delay, retinopathy and perceptive deafness are common to PBDs. PBD patients belonging to complementation group 3 (CG3) have mutations in the PEX12 gene, which codes for a protein (PEX12) that contains two transmembrane domains, and a zinc-binding domain considered to be important for its interaction with other proteins of the peroxisomal protein import machinery. We report on the identification of five PBD patients belonging to CG3. Sequence analysis of their PEX12 genes revealed five different mutations, four of which have not been reported before. Four of the patients have mutations that disrupt the translation frame and/or create an early termination codon in the PEX12 open reading frame predicted to result in truncated protein products, lacking at least the COOH-terminal zinc-binding domain. All these patients display the more severe phenotypes (ZS or NALD). The fifth patient expresses two PEX12 alleles capable of encoding a protein that does contain the zinc-binding domain and displayed a milder phenotype (IRD). The three biochemical markers measured in fibroblasts (DHAPAT activity, C26:0 beta-oxidation and pristanic acid beta-oxidation) also correlated with the genotypes. Thus, the genotypes of our CG3 patients show a good correlation with the biochemical and clinical phenotype of the patient

Incremental Evaluation Model for the Analysis of Indoor Air Measurements

The investigation of the cleaning effectiveness of air cleaners under realistic conditions is challenging. Mathematical models are needed to extract characteristic properties of the air cleaning system from experimental data. An incremental evaluation model based on a source term and a total first-order loss coefficient in each segment was developed to analyze indoor particle measurements. The application of the model is demonstrated using two scenarios, one in a well-mixed testing room and another in a fully equipped aircraft cabin at 750 hPa with a typical aircraft ventilation system. In the first scenario, a normalized version of the model is used to eliminate the source’s influence. For the investigation in the aircraft cabin, the model served to extract temporal and spatial resolved source terms and first-order loss coefficients. The incremental evaluation model is applicable to enhance the certification of air cleaners. The application of the model is not only limited to particles; measurements of gaseous compounds like ozone, carbon dioxide, or volatile organic compounds can be evaluated analogously. The model’s utility for the data analysis of experiments with complex flow conditions should be studied in further investigations