[Tuberculosis Contact Investigation: Eight Years of Experience with the QuantiFERON-TB®Gold In-Tube in Lower Saxony, Germany]. / Tuberkulose-Umgebungsuntersuchungen: Acht Jahre Erfahrung mit dem QuantiFERON-TB®Gold In-Tube in Niedersachsen.

Since the beginning of the 21st century, beside tuberculin skin tests (TST) and chest X-rays, interferon-gamma release assays (IGRA) have become available for diagnosing latent tuberculosis infection. In 2006, the Governmental Institute of Public Health of Lower Saxony (NLGA) established the IGRA in its laboratory, using the QuantiFERON-TB®Gold In-Tube (QFT). A cohort of 19 309 contact persons who were investigated during contact tracing by local public health departments (LPHD) was analyzed. Within 3 years, 75% of LPHDs in Lower Saxony established the QFT for tuberculosis contact tracing. Between 2007 and 2014 the percentage of contact persons≥15 years of age with initial TST declined from 65.1 to 1.7%. For contact persons<15 years of age, this proportion declined from 81.7% (2007) to 10.1% (2014). The proportion of contact persons who reported a country of birth outside Germany rose from 21.3 to 28.8% between 2008 and 2013. Cases from South Eastern European countries were increasingly reported, seldom from states of the former Soviet Union. 14.1% of the investigated contact persons had a positive QFT. 449 persons with a negative result underwent a second test within 4 months; 4% of these tested positive. Within a period of 8 years, the TST was replaced by the QFT in Lower Saxony, not least because of the modified recommendations for environmental contact tracing in tuberculosis of the German Central Committee against Tuberculosis (DZK). Higher specificity of the QFT and thus fewer X-rays, omission of the second visit for interpreting the TST, and the inappropriate package size of the TST for smaller LPHDs are further arguments in favor for the QFT. But unspecific use of the QFT must be avoided; otherwise, the value of the QFT result declines. The increasing number of contact persons with migration background and the changing countries of origin are a challenge for all who are involved in tuberculosis contact tracing.

Detection of a significant association between mutations in the ACVRL1 gene and hepatic involvement in German patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a heterogeneous multisystemic dysplasia of the vascular tissue. This autosomal dominant inherited disorder shows a wide variation in its phenotypic expression. Between 8 and 78% of the HHT patients show arteriovenous malformations of the liver. The molecular basis for hepatic manifestation is still unknown. Two genes are known to play a major role in the development of HHT: activin A receptor type II-like 1 gene (ACVRL1) and ENG. Previously, we and others showed that hepatic involvement is associated with mutations in the ACVRL1 gene, but rarely caused by ENG mutations. Here, we report about the sequencing analysis of a new cohort of 18 adult HHT patients. In these patients, we identified eight novel (four in ACVRL1 and four in ENG) and eight already known mutations. Statistical analysis of our entire data revealed significant differences in the distribution of ACVRL1 and ENG mutations among HHT patients with and without liver involvement (p = 0.0016). The positive predictive value for type 2 HHT (ACVRL1 positive) patients to develop liver disease until the age of 52 years is 68.4%. We conclude that molecular genetic testing of HHT patients is important for prognosis with respect to liver disease.

Dyschromatosis universalis hereditaria: evidence for autosomal recessive inheritance and identification of a new locus on chromosome 12q21-q23.

Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria (DSH) are pigmentary dermatoses most commonly seen in Japan. Both disorders usually show autosomal dominant inheritance, although in some cases autosomal recessive inheritance was reported. DSH was mapped to chromosome 1q21.3, and mutations in the gene ADAR (DSRAD) were identified in Japanese, Chinese and Taiwanese families with autosomal dominant DSH. A second locus for dyschromatosis was mapped on chromosome 6q24.2-q25.2 in two Chinese families initially reported to be affected with DSH, but later suggested to have autosomal dominant DUH. The aim of this study was to investigate whether one of these two loci is involved in the development of DUH in a consanguineous Bedouin family from Saudi Arabia with four affected and three unaffected sibs, clearly pointing to autosomal recessive inheritance. After excluding mutations in ADAR and linkage to the candidate regions on chromosomes 1 and 6, we performed an single nucleotide polymorphism-based genome-wide scan for linkage with other loci. Under the assumption of autosomal recessive inheritance, we have identified a new locus for dyschromatosis on chromosome 12q21-q23 in this Arab family with a maximum logarithm of the odds (LOD) score of 3.4, spanning a distance of 18.9 cM. Our study revealed the first locus for autosomal recessive DUH and supports recent evidence that DSH and DUH are genetically distinct disorders.