Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2007
Franziska Schnabel
{"title":"Aufbau eines neuen Patientenregisters für Gorlin-Goltz-Syndrom.","authors":"Franziska Schnabel","doi":"10.1515/medgen-2023-2007","DOIUrl":"10.1515/medgen-2023-2007","url":null,"abstract":"","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"79-80"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45097295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2010
Ingo Marenholz, Aleix Arnau-Soler, Oscar Daniel Rosillo-Salazar, Young-Ae Lee
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.
{"title":"New insights from genetic studies of eczema.","authors":"Ingo Marenholz, Aleix Arnau-Soler, Oscar Daniel Rosillo-Salazar, Young-Ae Lee","doi":"10.1515/medgen-2023-2010","DOIUrl":"10.1515/medgen-2023-2010","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"33-45"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43655018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2004
F Buket Basmanav, Regina C Betz
Alopecia areata (AA) is a common autoimmune-mediated hair loss disorder in humans with an estimated lifetime risk of approximately 2 %. Episodes of hair loss usually begin with isolated hairless patches that may progress to complete hair loss over the entire body. A familial occurrence of AA is well established, with recurrence risks of about 6-8 % in first-degree relatives. AA is a multifactorial disorder involving both environmental and genetic risk factors. Previous research has identified 14 susceptibility loci, most of which implicate genes involved in the immune response. The following review presents a summary of the latest findings from genome-wide association, sequencing and gene expression studies of AA, as well as their contribution to the recent therapeutic developments.
{"title":"Recent advances in the genetics of alopecia areata.","authors":"F Buket Basmanav, Regina C Betz","doi":"10.1515/medgen-2023-2004","DOIUrl":"10.1515/medgen-2023-2004","url":null,"abstract":"<p><p>Alopecia areata (AA) is a common autoimmune-mediated hair loss disorder in humans with an estimated lifetime risk of approximately 2 %. Episodes of hair loss usually begin with isolated hairless patches that may progress to complete hair loss over the entire body. A familial occurrence of AA is well established, with recurrence risks of about 6-8 % in first-degree relatives. AA is a multifactorial disorder involving both environmental and genetic risk factors. Previous research has identified 14 susceptibility loci, most of which implicate genes involved in the immune response. The following review presents a summary of the latest findings from genome-wide association, sequencing and gene expression studies of AA, as well as their contribution to the recent therapeutic developments.</p>","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"15-22"},"PeriodicalIF":0.8,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43680226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2009
Regina C Betz, Ulrike Hüffmeier
{"title":"Dermatological diseases from a genetic perspective.","authors":"Regina C Betz, Ulrike Hüffmeier","doi":"10.1515/medgen-2023-2009","DOIUrl":"10.1515/medgen-2023-2009","url":null,"abstract":"","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"1-2"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48645581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2003
Sabrina K Henne, Markus M Nöthen, Stefanie Heilmann-Heimbach
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.
{"title":"Male-pattern hair loss: Comprehensive identification of the associated genes as a basis for understanding pathophysiology.","authors":"Sabrina K Henne, Markus M Nöthen, Stefanie Heilmann-Heimbach","doi":"10.1515/medgen-2023-2003","DOIUrl":"10.1515/medgen-2023-2003","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"3-14"},"PeriodicalIF":0.8,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46590524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2005
Ulrike Hüffmeier, Janine Klima, Mohammad Deen Hayatu
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.
{"title":"Genetic underpinnings of the psoriatic spectrum.","authors":"Ulrike Hüffmeier, Janine Klima, Mohammad Deen Hayatu","doi":"10.1515/medgen-2023-2005","DOIUrl":"10.1515/medgen-2023-2005","url":null,"abstract":"<p><p>The psoriatic field includes both rare and common subtypes. Common complex forms include psoriasis vulgaris and psoriatic arthritis. In these subtypes, certain <i>HLA</i> 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.</p>","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"46-54"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46306345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2001
Tiemo Grimm, Klaus Zerres
{"title":"Holger Höhn zum 80. Geburtstag und der mühsame Beginn der Humangenetik in Würzburg vor mehr als 40 Jahren.","authors":"Tiemo Grimm, Klaus Zerres","doi":"10.1515/medgen-2023-2001","DOIUrl":"10.1515/medgen-2023-2001","url":null,"abstract":"","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"55-60"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46389264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2002
Gabriele Gillessen-Kaesbach
{"title":"Nachruf Prof. Dr. med. Eberhard Schwinger.","authors":"Gabriele Gillessen-Kaesbach","doi":"10.1515/medgen-2023-2002","DOIUrl":"10.1515/medgen-2023-2002","url":null,"abstract":"","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"61-62"},"PeriodicalIF":1.1,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47437202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-05eCollection Date: 2023-04-01DOI: 10.1515/medgen-2023-2006
Judith Fischer, Alrun Hotz, Katalin Komlosi
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.
遗传性鱼鳞病被归类为孟德尔角化障碍(Mendelian disorders of cornification, MEDOC),在临床和遗传特征的基础上进一步定义,可分为非综合征型和综合征型。迄今为止,已知30多个基因的突变可导致各种类型的综合征性鱼鳞病,除了皮肤普遍起鳞和角化过度外,还表现出额外的器官受损伤。综合征型鱼鳞病通常非常罕见,根据遗传方式分类,并可根据主要症状进一步细分。在我们的回顾中,我们提供了每个亚组中最常见的鱼鳞病综合征形式的简明概述。我们强调复杂综合征的临床评估的重要性,即使在基因检测作为一级诊断的时代,特别是需要积极评估鱼鳞病患者潜在的器官累及,从而实现有效的诊断和治疗方法,并及时进入罕见的专业化中心。作为弗赖堡罕见病中心的一部分,最近在人类遗传学研究所和皮肤病学部门的合作下建立了一个锥体化疾病中心。综合征的早期诊断将直接有利于患者的介入和治疗措施,例如:在涉及心脏或代谢的综合征中,允许知情的生殖选择,并在家庭中获得产前和植入前遗传学诊断。
{"title":"Syndromic ichthyoses.","authors":"Judith Fischer, Alrun Hotz, Katalin Komlosi","doi":"10.1515/medgen-2023-2006","DOIUrl":"10.1515/medgen-2023-2006","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":48632,"journal":{"name":"Medizinische Genetik","volume":"35 1","pages":"23-32"},"PeriodicalIF":0.8,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48573593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}