Skeletal Disorders and Genetic Syndromes Working Group
The Skeletal Disorders and Genetic Syndromes working group is headed by Prof. Dr. Christian Netzer. It includes staff working in molecular genetic diagnostics at the Institute and primarily addresses questions in routine diagnostics using state-of-the-art technologies. In 2019, the working group, together with an international team of scientists, described a new syndrome associated with premature ageing and provided genetic clarification for it. A focus of recent research has been brittle bone disease (osteogenesis imperfecta; OI), a genetic skeletal disease that results in increased fragility of the bones. Using next-generation sequencing, we have been able to identify the genes that cause OI types V and VI that researchers have been seeking for a long time. In this project, we have been working closely with the OI Outpatient Center at the Clinic and Polyclinic for Paediatric and Adolescent Medicine at the University Hospital Cologne (Assistant Prof. Dr. O. Semler, Prof. Dr. E. Schönau). With a translational research approach, these new molecular findings on the pathogenesis of OI are also being used to develop new therapies. This has led to the first use of the RANKL antibody denosumab in children with brittle bone disease.
Another research focus addresses issues of medical ethics that are arising as a result of the rapid progress being made in human genetics.
Moosa S, Yamamoto GL, Garbes L, Keupp K, Beleza-Meireles A, Moreno CA, Valadares ER, de Sousa SB, Maia S, Saraiva J, Honjo RS, Kim CA, Cabral de Menezes H, Lausch E, Lorini PV, Lamounier A Jr, Carniero TCB, Giunta C, Rohrbach M, Janner M, Semler O, Beleggia F, Li Y, Yigit G, Reintjes N, Altmüller J, Nürnberg P, Cavalcanti DP, Zabel B, Warman ML, Bertola DR, Wollnik B, Netzer C.
Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta.
Am J Hum Genet. 2019 Oct 3;105(4):836-843.
PubMed PMID: 31564437
Marbach F, Rustad CF, Riess A, Đukić D, Hsieh TC, Jobani I, Prescott T, Bevot A, Erger F, Houge G, Redfors M, Altmueller J, Stokowy T, Gilissen C, Kubisch C, Scarano E, Mazzanti L, Fiskerstrand T, Krawitz PM, Lessel D, Netzer C.
The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial Phenotyping.
Am J Hum Genet. 2019;104(4):749-757.
Pubmed PMID: 30905398
Hoyer-Kuhn H, Rehberg M, Netzer C, Schoenau E, Semler O.
Individualized treatment with denosumab in children with osteogenesis imperfecta - follow up of a trial cohort.
Orphanet J Rare Dis. 2019 Sep 18;14(1):219.
PubMed PMID: 31533771
Riehmer V, Erger F, Herkenrath P, Seland S, Jackels M, Wiater A, Heller R, Beck BB, Netzer C.
A heritable microduplication encompassing TBL1XR1 causes a genomic sister-disorder for the 3q26.32 microdeletion syndrome.
Am J Med Genet A. 2017;173(8):2132-2138.
PubMed PMID: 28574232
Garbes L, Kim K, Rieß A, Hoyer-Kuhn H, Beleggia F, Bevot A, Kim MJ, Huh YH, Kweon HS, Savarirayan R, Amor D, Kakadia PM, Lindig T, Kagan KO, Becker J, Boyadjiev SA, Wollnik B, Semler O, Bohlander SK, Kim J, Netzer C.
Mutations in SEC24D, Encoding a Component of the COPII Machinery, Cause a Syndromic Form of OsteogenesisImperfecta.
Am J Hum Genet. 2015:5;96(3):432-9.
Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E.
First use of the RANKL antibody denosumab in Osteogenesis Imperfecta Type VI.
J Musculoskelet Neuronal Interact. 2012 Sep;12(3):183-8.
PubMed PMID: 22947550
Semler O, Garbes L, Keupp K, Swan D, Zimmermann K, Becker J, Iden S, Wirth B, Eysel P, Koerber F, Schoenau E, Bohlander SK, Wollnik B, Netzer C.
A Mutation in the 5'-UTR of IFITM5 Creates an In-Frame Start Codon and Causes Autosomal-Dominant Osteogenesis Imperfecta Type V with Hyperplastic Callus.
Am J Hum Genet. 2012 Aug 10;91(2):349-57. Epub 2012 Aug 2.
PubMed PMID: 22863195
Netzer C, Schmitz D, Henn W.
To know or not to know the genomic sequence of a fetus.
Nat Rev Genet. 2012 Oct;13(10):676-7. doi: 10.1038/nrg3333. Epub 2012 Sep 4.
PubMed PMID: 22945393
Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, Bergmann C, Rohrbach M, Koerber F, Zimmermann K, de Vries P, Wirth B, Schoenau E, Wollnik B, Veltman JA, Hoischen A, Netzer C.
Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta.
Am J Hum Genet. 2011, 88:362-71.
PubMed PMID: 21353196
Prof. Christian Netzer, MD, has been Manager of Clinical Human Genetics since 2019. Previously, he served as a Senior Physician at the Institute of Human Genetics and since 2009 was Head of Human Genetics at the Medical Health Center (Medizinische Versorgungszentrum, MVZ) at the University Hospital Cologne. Prof. Netzer completed his post-doctoral professorship and research qualification at the University of Cologne in 2009 with his work on the molecular pathogenesis of monogenic diseases and since then his research has focussed on the genetic causes of hereditary skeletal diseases and syndromes. For his research, in 2012 he received the Eva Luise Köhler Research Award for Rare Diseases. Following further training at the Institutes for Human Genetics at the Universities of Göttingen and Bonn, in 2005 he became a specialist in Human Genetics. Prof. Netzer studied medicine and philosophy in Göttingen and Hamburg. He completed his doctorate at the University of Göttingen; he also received an MA in philosophy there, completing his work on the moral issue pre-implantation diagnostics.
In 2018, Prof. Netzer was appointed to the Gene Diagnostics Committee of the RKI by the Federal Health Ministry. He is the deputy spokesperson of the committee for Fundamental Positions and Ethics Issues of the Germany Society for Human Genetics (Deutsche Gesellschaft für Humangenetik, GfH).
Jutta Becker, PhD, specialist in human genetics
Serjoscha Blick, biological-technical assistant
Nico Fuhrmann, PhD, specialist in human genetics
Dr. rer. nat. Sophie Kaspar, M.Sc., research associate
Katharina Nohl, biological-technical assistant
Nadine Reintjes, PhD, specialist in human genetics
Vera Riehmer, PhD, specialist in human genetics
Saskia Seland, biological-technical assistant
Laura Wilden, biological-technical assistant