Medizinische Genetik最新文献

Genome-wide association studies (GWAS) provided fundamental insight into the genetic determinants of complex allergic diseases. For eczema, 58 susceptibility loci were reported. Protein-changing variants were associated with eczema at genome-wide significance at 12 loci. The majority of risk variants were, however, located in non-coding, regulatory regions of the genome. Prioritized target genes were enriched in pathways of the immune response and of epithelial barrier function. Interestingly, a large overlap in the genetic architecture underlying different allergic diseases was identified pointing to common pathomechanisms for eczema, asthma, hay fever, and food allergy. Here, we review the most recent findings from GWAS for eczema including the role of rare variants and genetic heterogeneity in ethnically diverse populations. In addition, we provide an overview of genes underlying Mendelian disorders featuring eczematous skin inflammation.

Male-pattern hair loss (MPHL) is a highly heritable and prevalent condition that is characterized by progressive hair loss from the frontotemporal and vertex scalp. This androgen-dependent hair loss may commence during puberty, and up to 80 % of European men experience some degree of MPHL during their lifetime. Current treatment options for MPHL have limited efficacy, and improved understanding of the underlying biological causes is required to facilitate novel therapeutic approaches. To date, molecular genetic studies have identified 389 associated genomic regions, have implicated numerous genes in these regions, and suggested pathways that are likely to contribute to key pathophysiological mechanisms in MPHL. This review provides an overview of the current status of MPHL genetic research. We discuss the most significant achievements, current challenges, and anticipated developments in the field, as well as their potential to advance our understanding of hair (loss) biology, and to improve hair loss prediction and treatment.

The psoriatic field includes both rare and common subtypes. Common complex forms include psoriasis vulgaris and psoriatic arthritis. In these subtypes, certain HLA alleles remain the most relevant genetic factors, although genome-wide association studies lead to the detection of more than 80 susceptibility loci. They mainly affect innate and adaptive immunity and explain over 28 % of the heritability. Pustular psoriasis comprises a group of rarer subtypes. Using exome sequencing, several disease genes were identified for mainly generalized pustular psoriasis, and an oligogenic inheritance is likely. Treatment studies based on the affected IL-36 pathway indicate a high response rate in this subtype further supporting the pathophysiological relevance of the affected gene products.

Inherited ichthyoses are classified as Mendelian disorders of cornification (MEDOC), which are further defined on the basis of clinical and genetic features and can be divided into non-syndromic and syndromic forms. To date, mutations in more than 30 genes are known to result in various types of syndromic ichthyoses, which, in addition to mostly generalised scaling and hyperkeratosis of the skin, also show additional organ involvement. The syndromic ichthyoses are generally very rare and are classified based on the mode of inheritance, and can be further subdivided according to the predominant symptoms. In our review we provide a concise overview of the most prevalent syndromic forms of ichthyosis within each subgroup. We emphasize the importance of the clinical assessment of complex syndromes even in the era of genetic testing as a first-tier diagnostic and specifically the need to actively assess potential organ involvement in patients with ichthyosis, thereby enabling efficient diagnostic and therapeutic approaches and timely access to specialized centers for rare disorders of cornifications. As part of the Freiburg Center for Rare Diseases a Center for Cornification Disorders was recently established with collaboration of the Institute of Human Genetics and the Department of Dermatology. An early diagnosis of syndromes will be of direct benefit to the patient regarding interventional and therapeutic measures e. g. in syndromes with cardiac or metabolic involvement and allows informed reproductive options and access to prenatal and preimplantation genetic diagnosis in the family.