Recessive Dystrophic Epidermolysis bullosa due to Hemizygous 40 kb Deletion of COL7A1 and the Proximate PFKFB4 Gene Focusing on the Mutation c.425A>G Mimicking Homozygous Status

Background: Dystrophic Epidermolysis bullosa (DEB) is a rare inherited mechanobullous disease characterised by the hyperfragility of the skin and mucous membranes. It is (typically) caused by (loss-of-function) mutations in the COL7A1 gene that impair the formation of collagen type VII, which represents the major constituent of anchoring fibrils within the basement membrane zone of epithelialised tissues. In a 4-year-old patient diagnosed with the clinical features of recessive DEB, genotyping via Next-Generation EB Panel Sequencing initially revealed the homozygosity of the maternal c.425A>G mutation, while the paternal heterozygosity in exon 3 was lacking. This genetic profile suggested incongruent gene transmission due to uniparental isodisomy (UPD) or the occurrence of a hemizygous deletion of unknown size. Methods: Thus, the EB panel sequencing of genomic DNA, followed by a paternity test and analysis of microsatellite markers, as well as multiplex ligation-dependent probe amplification (MLPA) copy number analysis using patient and parental DNA, were performed. Results: This approach revealed a paternally derived hemizygous deletion spanning from exon 3 to exon 118. Linear amplification-mediated PCR (LAM-PCR) determined the breaking points within intron 2 of the COL7A1 gene, comprising a 40kb segment within intron 1 of the adjacent PFKFB4 gene. Conclusion: This report highlights the relevance of advanced molecular profiling to determine new/exceptional/unusual genotypes and the accurate mode of genetic transmission in DEB.

Introduction of Chlamydia trachomatis screening for young women in Germany.

Screening for genital Chlamydia trachomatis infections for young sexually active women was incorporated into routine medical care of German statutory health insured patients starting in January 2008. The primary goal of this new preventive measure is the reduction of severe sequelae for women such as tubal infertility and ectopic pregnancies. The course of the deliberations leading to the Federal Joint Committee's decision is summarized in this review.

[Positron emission tomography--a technique for the routine practice of ambulatory care?]. / Positronen Emissions Tomographie--eine Technik für die Routineanwendung in der ambulanten Versorgung?

Positron Emission Tomography (PET) has been regarded as a breakthrough technology that helps diagnoses various conditions. PET was developed in the United States during the 1960s, and has since diffused rather slowly into most modern health care systems. Germany is an exception, as here the diffusion of PET has been rapid, and more than 70 PET scanners have been installed. At present, PET scans are not included in the health care basket though they are often used and members of the statutory sickness fund frequently seek reimbursement for this technology. The Standing Committee therefore conducted a formal inquiry into the value of PET scanning in publicly funded (statutory) ambulatory health care. The Committee's decisions were based on a technology assessment of PET. This report found that PET has been approved by the German Federal Institute for Drugs and Medical Devices (BfArM) for five indications. The evidence for these five indications was compared to that for other diagnostic methods such as magnetic resonance imaging. The assessment found no convincing evidence to support the introduction of PET into statutory ambulatory health care in Germany. In April 2002 the Standing Committee consequently denied approval for the reimbursement of PET as a publicly funded diagnostic procedure.