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An outbreak with a remarkable Listeria monocytogenes clone causing 163 cases of non-invasive listeriosis occurred in Germany in 2015. Core genome multi locus sequence typing grouped non-invasive outbreak isolates and isolates obtained from related food samples into a single cluster, but clearly separated genetically close isolates obtained from invasive listeriosis cases. A comparative genomic approach identified a premature stop codon in the chiB gene, encoding one of the two L. monocytogenes chitinases, which clustered with disease outcome. Correction of this premature stop codon in one representative gastroenteritis outbreak isolate restored chitinase production, but effects in infection experiments were not found. While the exact role of chitinases in virulence of L. monocytogenes is still not fully understood, our results now clearly show that ChiB-derived activity is not required to establish L. monocytogenes gastroenteritis in humans. This limits a possible role of ChiB in human listeriosis to later steps of the infection.

Van der Woude syndrome (VWS) is the most common type of syndromic orofacial cleft, which accounts for approximately 2% of all cleft lip and palate cases. It is characterised by variable association of lower lip pits, cleft lip and cleft palate, and hypodontia. VWS arises as the result of mutations in the gene encoding interferon regulatory factor 6 (IRF6). The disorder is transmitted in an autosomal dominant manner, with high penetrance and variable expressivity. Very recently, mutations of the IRF6 gene in exons 2-9 have been found in VWS patients, suggesting that this gene plays an important role in orofacial development. We report a novel mutation of the IRF6 gene in a German family. Five out of the 12 persons affected were able to be investigated. The mutation produced a stop codon within exon 4 of the IRF6 gene. All 5 patients were heterozygous for a base substitution c.201C>A changing the tyrosine codon at amino acid position 67 into a stop codon (p.Y67X) in exon 4. The premature stop codon was responsible for a truncated protein lacking parts of the DNA- binding domain and the complete Smad-interferon regulatory factor-binding domain probably essential for interactions with the Smad transcription factors.

Sjögren-Larsson syndrome (SLS) is a rare autosomal recessively inherited disorder characterised by mental retardation, spasticity and ichthyosis. SLS patients have a profound deficiency in fatty aldehyde dehydrogenase (FALDH) activity. The human cDNA of FALDH has been shown to map to the SLS locus on chromosome 17p11.2. Here we describe a method based on reverse transcriptase-polymerase chain reaction (RT-PCR) and protein truncation test to identify mutations in the FALDH gene in nine German SLS families. Using this detection system both disease-causing mutations were found in eight of the nine SLS families examined (17/18 chromosomes). Seven different mutations were identified: an exon 2 skipping due to exon 2 splice donor mutation; two different exon 3 splice donor mutations resulting in combined exon 2 and 3 skipping; a 906delT deletion in exon 6; a genomic deletion of about 6 kb including exon 9; a 1277T > G transversion resulting in a Leu426Ter nonsense mutation; and a 1297delGA deletion. Two of the mutations identified, the genomic exon 9 deletion and the 906delT in exon 6 affected five out of seven SLS patients from a small region of Northern Bavaria. Therefore these two mutations accounted for 71% (10/14 chromosomes) of Bavarian SLS alleles and so far have not been described in SLS families from other countries. Our findings do not support our 'historical' hypothesis, that a possible region clustering in Northern Bavaria could be due to the presence of Swedish soldiers during the 30 Years War (1618-1648), but suggest that two mutations causing SLS syndrome originated in Northern Bavaria.

Type III hyperlipoproteinemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (Arg112 --> Cys, Arg158 --> Cys). This common apo E isoform is defective in its binding to lipoprotein receptors. However, other rare mutations in the apo epsilon gene may also, in part dominantly, predispose to the disease. In order to assess the prevalence of rare apo E variants and mutations in the apo epsilon gene in Germany, we examined apo epsilon genotypes by restriction isotyping (RI) and apo E phenotypes by isoelectric focusing (IEF) in 107 German patients with type III HLP. Concordance between apo epsilon genotype and apo E phenotype was observed in 101 subjects (94.4%). Six individuals (5.6%) had genotypes and phenotypes other than E2/2. One subject was apparently homozygous for apo E2 by IEF, but heterozygous for epsilon3/2 by RI. Sequencing of the apo epsilon gene disclosed a hitherto undescribed point mutation (TGG --> TGA) at the third position of the codon for amino acid 20 (Trp), introducing a premature termination codon. This is the first study demonstrating that in the German population type III HLP is mainly associated with homozygosity for apo E2 (Arg112 --> Cys, Arg158 --> Cys) and that discrepancies between apo epsilon genotype and apo E phenotype are rare in this genetic condition.

A stop codon in the precore genome of the hepatitis B virus (HBV) in anti-HBe positive HBV carriers may be associated with a more progressive form of HBV infection. Earlier studies, however, were mainly performed in patients from the Mediterranean area who had severe infection. The aim of this study was to evaluate the prevalence of precore mutants in an unselected population living in northern Europe. Twenty of 42 of these patients are infected predominantly with a virus strain, which has the typical stop codon in the precore genome, characterised by a mutation at base 83. In six patients there was an additional G to A mutation at base 86 of the precore genome. Statistical analysis showed no difference between the patients with or without a stop codon in the precore genome. When patients with a double mutation at base 83 and 86 of the precore genome were compared with the other anti-HBe positive HBV carriers, however, the corresponding clinical data were worse. Therefore we suggest, that it is not the stop codon in the precore gene itself, but the occurrence of a double mutation at bases 83 and 86, which is associated with a more severe course of disease in anti-HBe positive HBV carriers.