Autosomal recessive congenital ichthyosis caused by a pathogenic missense variant in CLDN1.

Autosomal recessive congenital ichthyosis (ARCI) refers to a large and genetically heterogenous group of non-syndromic disorders of cornification featuring diffuse scaling. Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome is a rare autosomal recessive syndromic form of ichthyosis. The disease usually results from premature termination codon-causing pathogenic variants in CLDN1 encoding CLAUDIN-1 (CLDN1). We used whole exome sequencing (WES), Sanger sequencing, 3D protein modeling, Western blotting, and immunofluorescence confocal microscopy to delineate the genetic basis of ichthyosis in two siblings with ichthyosis but no other ectodermal abnormalities. One of the two siblings underwent liver transplantation in early childhood due to biliary atresia. Both patients were found to carry a homozygous missense pathogenic variant, c.242G>A (p.Arg81His), in CLDN1. The variant resulted in decreased CLDN1 expression in patient skin. 3D protein modeling predicted that p.Arg81His induces deleterious conformational changes. Accordingly, HaCaT cells transfected with a construct expressing the mutant CLDN1 cDNA featured decreased levels and mislocation of CLDN1 as compared with cells expressing the wildtype cDNA. In conclusion, we describe the first pathogenic missense variant in CLDN1 shown to result in ARCI.

Staphylococcus aureus carrier state among elderly residents of a long-term care facility.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infections have recently become a major concern in long-term care facilities (LTCF). Patients that have been colonized with MRSA in general hospitals may introduce the organisms into LTCF, and these can become reservoirs for the pathogen. Our objective was to evaluate the rate of colonization by S aureus, especially MRSA, in elderly residents of a large LTCF, and to find factors that predispose to it. METHODS: A nasal culture was obtained from randomly selected patients in an Israeli LTCF. Inclusion criteria were absence of active infection and no antibiotic treatment in the preceding month. The carrier state was defined when two consecutive cultures were positive for S aureus. RESULTS: The study population comprised 270 patients, aged 81 +/- 9.3 years and from all types of wards. Of these, 63 (23.3%) were carriers of S aureus and 17 of those (27%) had MRSA. From univariate analysis, the carrier state was associated with antibiotic treatment or an invasive procedure in the previous 3 months, and with a prior MRSA infection. Subacute LTCF departments had a higher carrier rate than the chronic care wards. CONCLUSIONS: In this large multilevel facility, 6.2% of the patients were MRSA carriers, and came predominantly from the subacute departments, suggesting an influx from general hospitals. This information and the identification of factors associated with MRSA infection permit the development of an institutional infection control program.