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Alport syndrome (AS) is a hereditary kidney disorder of type IV collagen caused by pathogenic variants in the COL4A3, COL4A4 and COL4A5 genes. Previously several cases of digenic AS, caused by two pathogenic variants in two of the three COL4A genes, have been reported. Patients with digenic AS may present with a more severe phenotype compared to patients with single variants, depending on the percentage affected type IV trimeric collagen chain. We report a newly discovered case of trigenic AS. A 52-year-old female presented with hematuria at the age of 24 years and developed hypertension by the age of 30. Over the years she developed chronic kidney disease; the most recent eGFR was 44ml/min/1.73m2. She has symmetric high-tone sensorineural hearing loss. Full genetic analysis revealed a heterozygous pathogenic variant c.2691del in COL4A3, a heterozygous pathogenic variant c.1663dup in COL4A4, and a complete heterozygous deletion of COL4A5. We describe the first patient with AS caused by pathogenic variants in all three COL4A genes, designated trigenic AS. This case report emphasizes the importance of examining all three COL4A genes, even in patients with a mild Alport phenotype, for optimal follow-up of the patient and adequate genetic counseling of family members., (The Author(s). Published by S. Karger AG, Basel.)

The goal of this three-wave longitudinal study was to analyze foster parent stress and foster children's internalizing and externalizing behaviors in a transactional framework. Participants in this study were 237 children in foster care in the Netherlands with, mostly, long placement durations ( M =  56.86 months, SD  = 49.10 months). We examined concurrent, prospective unidirectional and bidirectional relations between foster children's behavior and foster parent stress by using cross-lagged structural equation modeling and examined whether the results were stable across different subgroups of foster children. In contrast to our hypothesis, we found no bidirectional relations. There were unidirectional prospective pathways from foster children's internalizing and externalizing problems to foster parent stress, but no significant prospective pathways from foster parent stress to foster children's internalizing and externalizing problems. The results were fairly stable across different subgroups of foster children. The lack of bidirectional relations was unexpected given the presence of transactional relations in biological parent-child dyads. Foster parents seem not to influence their foster children when it comes to regulating problem behavior. Therefore, the question is whether foster parents can, in more general terms, help their foster children benefit from their improved home environment., Competing Interests: Compliance with Ethical StandardsThe authors declare that they have no competing interests.The study was approved by the Leiden University Ethics Review Board. Number ECPW-2013-049. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.Informed consent was obtained from all individual participants included in the study.

Mal de Meleda (Mal de Mljet) is a recessive palmoplantar hyperkeratosis associated with hyperhidrosis, brachydactyly and sometimes pseudo-ainhum. It was recently discovered to be caused by mutations in the ARS gene on chromosome 8. Here we report a patient suffering from Mal de Meleda not associated with ARS mutations. The related E48 and GML genes were also excluded.