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Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa‐Like Domain‐Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

A solid-phase transfection platform for arrayed CRISPR screens The following sentence should have been included in the introduction: "A previously reported solid-phase reverse transfection method for proteins (Bulkescher I et al i , [1]) was used for the delivery of RNPs for three endogenous genes suggesting the potential of solid-phase reverse transfection for CRISPR/Cas9-based gene editing, despite its low efficiency". Reference 1 Bulkescher R, Starkuviene V, Erfle H (2017) Solid-phase reverse transfection for intracellular delivery of functionally active proteins. [Extracted from the article]

Arrayed CRISPR‐based screens emerge as a powerful alternative to pooled screens making it possible to investigate a wide range of cellular phenotypes that are typically not amenable to pooled screens. Here, we describe a solid‐phase transfection platform that enables CRISPR‐based genetic screens in arrayed format with flexible readouts. We demonstrate efficient gene knockout upon delivery of guide RNAs and Cas9/guide RNA ribonucleoprotein complexes into untransformed and cancer cell lines. In addition, we provide evidence that our platform can be easily adapted to high‐throughput screens and we use this approach to study oncogene addiction in tumor cells. Finally demonstrating that the human primary cells can also be edited using this method, we pave the way for rapid testing of potential targeted therapies. Synopsis: This study presents a solid phase transfection platform that enables CRISPR‐based genetic screens in arrayed format with flexible readouts. Solid phase transfection of gRNAs or RNPs is applicable to a wide variety of cell lines.Solid phase transfection can be easily adapted to high throughput screens.A demonstration that human primary cells can be edited using this platform, indicates the potential of the approach for rapid testing of candidate targeted therapies. [ABSTRACT FROM AUTHOR]