[Alban Köhler - A review of his 150th birthday based on his "memoirs" and his X-ray books].

150 years ago, on March 1, 1874, Prof. Dr. Alban Köhler, pioneer in X-ray diagnostics and Co-founder of the German Radiological Society, was born.

The interplay of chronic stress and genetic traits discriminates between patients suffering from multisomatoform disorder with pain as the leading symptom and matched controls.

Objective: Somatoform disorders and functional somatic syndromes (FSS) with symptoms that are not sufficiently explained by physical or technical examination are among the most challenging underlying causes. Many different somatoform disorders and FSS have overlapping symptoms, often with pain as the most prevalent one, leading to a high burden of disease. The concept of multisomatoform disorder (MSD) has been developed to acknowledge that fact.

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions.

Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data.

NCAM2 deletion in a boy with macrocephaly and autism: Cause, association or predisposition?

Unlabelled: We report on an 8-year-old boy with autism spectrum disorder (ASD), speech delay, behavioural problems, disturbed sleep and macrosomia including macrocephaly carrying a microdeletion that contains the entire NCAM2 gene and no other functional genes. Other family members with the microdeletion show a large skull circumference but do not exhibit any symptoms of autism spectrum disorder. Among many ASD-candidate genes, NCAM2 has been assumed to play a pivotal role in the development of ASD because of its function in the outgrowth and bundling of neurites.

Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort.

Background: Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations.

Methods: We screened a Danish cohort of 243 GTS patients and 1571 control subjects for submicroscopic deletions and duplications of these four genes.

Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy.

Background: Hypertrophic cardiomyopathy (HCM) is caused by mutations in different structural genes and induces pathological hypertrophy with sudden cardiac death as a possible consequence. HCM can be separated into hypertrophic non-obstructive and obstructive cardiomyopathy (HNCM/HOCM) with different clinical treatment approaches. We here distinguished between HNCM, HOCM, cardiac amyloidosis and aortic stenosis by using microRNA profiling and investigated potential interactions between circulating miRNA levels and the most common mutations in MYH7and MYBPC3 genes.

Variants in TSPYL1 are not associated with sudden infant death syndrome in a cohort of deceased infants from Switzerland.

Sudden infant death syndrome (SIDS) is currently the major cause of an unexpected and unexplained death of infants in the first year of lifetime in industrialized countries. Besides environmental factors also genetic factors have been identified as risk factors for SIDS. Notably, the mutation c.

Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients.

Background: Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia.

Genetic association signal near NTN4 in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.

CFTR, SPINK1, PRSS1, and CTRC mutations are not associated with pancreatic cancer in German patients.

Objective: Mutations in the cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1), and chymotrypsin C (CTRC) genes are associated with an elevated risk for chronic pancreatitis, which is a known risk factor for pancreatic cancer (PC). Therefore, we analyzed whether PRSS1, CFTR, SPINK1, and/or CTRC mutations are associated with pancreatic adenocarcinoma.

Methods: The study cohort was composed of 121 PC patients, of whom 74 were classified as having chronic pancreatitis, 102 patients with idiopathic chronic pancreatitis, and 130 as healthy controls.

1,25-Dihydroxyvitamin D decreases HTRA1 promoter activity in the rhesus monkey--a plausible explanation for the influence of vitamin D on age-related macular degeneration?

Age-related macular degeneration is the major cause of blindness in the elderly worldwide and the risk is influenced by both environmental and genetic risk factors. One important disease-associated region in humans is located on 10q26 and includes the two candidate genes ARMS2 and HTRA1. However, determination of the causative gene has not yet been possible and examining the situation in the rhesus monkey may help understand the situation in humans.

Association of TNF-α polymorphism rs1800629 with multisomatoform disorder in a group of German patients and healthy controls: an explorative study.

Introduction: The etiology of multisomatoform disorder (MSD) is still largely unknown, but genetic factors seem to have an influence on pathogenesis. Pain is a major symptom of MSD and polymorphisms of different proinflammatory cytokines have been found associated with pain in former studies. Therefore, we presumed that cytokine polymorphisms could also be associated with MSD.

High-density oligonucleotide-based resequencing assay for mutations causing syndromic and non-syndromic forms of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection is associated with increasing mortality rate that may occur as part of a syndrome or as an isolated familial condition. Several genes have been implicated in causing TAAD, though an appropriate genetic test for their parallel testing is not yet available. Herein, we describe the novel 117-kb "MFSTAAD chip" that may help to understand the genetic basis of TAAD.

Interaction of the dopaminergic and serotonergic systems significantly influences the risk for multisomatoform disorder: a controlled pilot study.

The etiology of multisomatoform disorder (MSD) is largely unknown, but an influence of genetic factors is likely. Since pain is a major component of MSD and dopamine as well as serotonin are involved in pain pathways, genes of the dopaminergic and serotonergic system are promising candidate genes and we assumed that polymorphisms could be associated with MSD. One hundred forty-nine patients with MSD and 149 age- and gender-matched healthy controls participated in this study.

Improvement of interpretation in cystic fibrosis clinical laboratory reports: longitudinal analysis of external quality assessment data.

Participation in external quality assessment (EQA) is a key element of quality assurance in medical laboratories. In genetics EQA, both genotyping and interpretation are assessed. We aimed to analyse changes in the completeness of interpretation in clinical laboratory reports of the European cystic fibrosis EQA scheme and to investigate the effect of the number of previous participations, laboratory accreditation/certification status, setting and test volume.

Diagnosis of hereditary hemochromatosis in the era of genetic testing.

Background: Homozygous C282Y mutation in HFE gene is responsible for the majority of hereditary hemochromatosis cases. Since 1996 this mutation can be identified by a simple genetic test.

Aims: To determine the clinical presentations in patients with homozygous HFE C282Y mutation and the impact of genetic testing on the time needed for diagnosis.

A novel GJC2 mutation associated with hypomyelination and Müllerian agenesis syndrome: coincidence or a new entity?

In recent years, several new white matter diseases have been identified based on magnetic resonance imaging and clinical findings. For most newly defined disorders the genetic basis has been identified. However, there is still a large group of patients without a specific diagnosis.

Characterization of the 10q26-orthologue in rhesus monkeys corroborates a functional connection between ARMS2 and HTRA1.

Age-related macular degeneration, which is the leading cause of blindness in industrialized countries, is a multifactorial, degenerative disorder of the macula with strong heritability. For age-related macular degeneration in humans, the genes ARMS2 and HTRA1 in the region 10q26 are both promising candidates for being involved in pathogenesis. However, the associated variants are located in a region of strong linkage disequilibrium and so far, the identification of the causative gene in humans was not yet possible.

Homozygous CFTR mutation M348K in a boy with respiratory symptoms and failure to thrive. Disease-causing mutation or benign alteration?

Unlabelled: We report on a 6-month-old premature boy from consanguineous parents. He presented with respiratory distress, necrotizing enterocolitis and hyperbilirubinemia shortly after birth. Persisting respiratory symptoms and failure to thrive prompted cystic fibrosis diagnostics, which showed the lack of wild-type signal for the mutation R347P suggesting a homozygous deletion or an alteration different from the known mutation at this position.

Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?

Objective: To investigate a putative role of TSPYL1 in male idiopathic infertility.

Design: Clinical article.

Setting: University hospital.

Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome.

Marfan syndrome is considered a clinical diagnosis. Three diagnostic classifications comprising first, Marfan genotype with a causative FBN1 gene mutation; second, Marfan phenotype with clinical criteria of the original Ghent nosology (Ghent-1); and third, phenotype with clinical criteria of its current revision (Ghent-2) in 300 consecutive persons referred for confirmation or exclusion of Marfan syndrome (150 men, 150 women aged 35 ± 13 years) were used. Sequencing of TGBR1/2 genes was performed in 128 persons without FBN1 mutation.