Diagnostik
Afdelingen udfører diagnostik for følgende imprintningssygdomme for danske og udenlandske rekvirenter:
Genetisk rådgivning
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Analyser
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Forskning
Forskningen i imprintningssygdomme er fokuseret på at identificere de genetiske/epigenetiske mekanismer hos patienter uden kendt årsag til deres imprintningssygdom. Afdelingens forskergruppe i imprintningssygdomme har identificeret deletion af H19 enhancer som en ny ætiologisk mekanisme ved SRS (Grønskov et al. 2011).
Ved et internationalt samarbejde har afdelingens forskergruppe i mprintningssygdomme medvirket til at identificere mutationer i ZFP57 genet som den genetiske årsag til TNDM (Transient Neonatal Diabetes Mellitus) med multipel hypometylering hos en gruppe af patienter med ved (Boonen et al. 2013, Mackay et al. 2008, Boonen et al. 2008,Boonen et al. 2006, Mackay et al. 2006,)
Afdelingen indgik i et europæisk netværk, EUCID, European Network for Human Congenital Imprinting Disorders, BMBS COST Action BM1208 (Eggermann et al. 2015 PMID 25784961), hvilket resulteret i to artikler om diagnostik og behandling af hhv. Silver-Russell syndrom (SRS) og Beckwith-Wiedemann syndrom (BWS) publiceret i Nature Reviews Endocrinology i hhv 2017 (PMID: 27585961) og 2018 (PMID: 29377879). Desuden i 2023 er afdelingen med i et nyt europæisk netværk støttet af EJP (Euorpean Joint Program) Rare Diseases til at udarbejde en vejledning til diagnostik og behandling af Multi-locus imprintningssygdomme (MLID) ( Diagnosis and management of Multi-locus Imprinting Disorders: Developing an International Expert Consensus).
Publikationer fra afdelingen
- Eggermann T, Monk D, de Nanclares GP, Kagami M, Giabicani E, Riccio A, Tümer Z, Kalish JM, Tauber M, Duis J, Weksberg R, Maher ER, Begemann M, Elbracht M.
Imprinting disorders. Nat Rev Dis Primers. 2023 Jun 29;9(1):33. doi: 10.1038/s41572-023-00443-4. PMID: 37386011.
- Stoltze UK, Hildonen M, Hansen TVO, Foss-Skiftesvik J, Byrjalsen A, Lundsgaard M, Pignata L, Grønskov K, Tumer Z, Schmiegelow K, Brok JS, Wadt KAW.
Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort. J Med Genet. 2023 Apr 5:jmg-2022-108982. doi: 10.1136/jmg-2022-108982. Epub ahead of print. PMID: 37019617.
- Stoltze UK, Hansen TVO, Brok JS, Grønskov K, Tumer Z, Ahlborn LB, Schmiegelow K, Wadt KAW.
Maternal versus paternal inheritance of a 132 bp 11p15.5 microdeletion affecting KCNQ1OT1 and associated phenotypes. J Med Genet. 2023 Feb;60(2):128-130. doi: 10.1136/jmedgenet-2021-108335. Epub 2022 Jun 30. PMID: 35772845; PMCID: PMC9887393.
- Mackay D, Bliek J, Kagami M, Tenorio-Castano J, Pereda A, Brioude F, Netchine I, Papingi D, de Franco E, Lever M, Sillibourne J, Lombardi P, Gaston V, Tauber M, Diene G, Bieth E, Fernandez L, Nevado J, Tümer Z, Riccio A, Maher ER, Beygo J, Tannorella P, Russo S, de Nanclares GP, Temple IK, Ogata T, Lapunzina P, Eggermann T. First step towards a consensus strategy for multi-locus diagnostic testing of imprinting disorders.
Clin Epigenetics. 2022 Nov 7;14(1):143. doi: 10.1186/s13148-022-01358-9. PMID: 36345041; PMCID: PMC9641836.
- Eggermann T, Yapici E, Bliek J, Pereda A, Begemann M, Russo S, Tannorella P, Calzari L, de Nanclares GP, Lombardi P, Temple IK, Mackay D, Riccio A, Kagami M, Ogata T, Lapunzina P, Monk D, Maher ER, Tümer Z.
Trans-acting genetic variants causing multilocus imprinting disturbance (MLID): common mechanisms and consequences. Clin Epigenetics. 2022 Mar 16;14(1):41. doi: 10.1186/s13148-022-01259-x. PMID: 35296332; PMCID: PMC8928698.
- Hjortshøj TD, Sørensen AR, Yusibova M, Hansen BM, Dunø M, Balslev-Harder M, Grønskov K, van Hagen JM, Polstra AM, Eggermann T, Finken MJJ, Tümer Z.
upd(20)mat is a rare cause of the Silver-Russell-syndrome-like phenotype: Two unrelated cases and screening of large cohorts. Clin Genet. 2020 Jun;97(6):902-907. doi: 10.1111/cge.13727. Epub 2020 Mar 11. PMID: 32087029.
- Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Õunap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skórka A, Tatton-Brown K, Tenorio J, Tortora C, Grønskov K, Netchine I, Hennekam RC, Prawitt D, Tümer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER.
Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018 Apr;14(4):229-249. doi: 10.1038/nrendo.2017.166. Epub 2018 Jan 29. PMID: 29377879; PMCID: PMC6022848.
- Tümer Z, López-Hernández JA, Netchine I, Elbracht M, Grønskov K, Gede LB, Sachwitz J, den Dunnen JT, Eggermann T.
Structural and sequence variants in patients with Silver-Russell syndrome or similar features-Curation of a disease database. Hum Mutat. 2018 Mar;39(3):345-364. doi: 10.1002/humu.23382. Epub 2018 Jan 11. PMID: 29250858.
- Monk D, Morales J, den Dunnen JT, Russo S, Court F, Prawitt D, Eggermann T, Beygo J, Buiting K, Tümer Z; Nomenclature group of the European Network for Human Congenital Imprinting Disorders. Recommendations for a nomenclature system for reporting methylation aberrations in imprinted domains. Epigenetics. 2018;13(2):117-121. doi: 10.1080/15592294.2016.1264561. Epub 2018 Jan 25. PMID: 27911167; PMCID: PMC5873357.
- Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017 Feb;13(2):105-124. doi: 10.1038/nrendo.2016.138. Epub 2016 Sep 2. PMID: 27585961.
- Soellner L, Begemann M, Mackay DJ, Grønskov K, Tümer Z, Maher ER, Temple IK, Monk D, Riccio A, Linglart A, Netchine I, Eggermann T.
Recent Advances in Imprinting Disorders. Clin Genet. 2017 Jan;91(1):3-13. doi: 10.1111/cge.12827. Epub 2016 Aug 4. PMID: 27363536.
- Eggermann K, Bliek J, Brioude F, Algar E, Buiting K, Russo S, Tümer Z, Monk D, Moore G, Antoniadi T, Macdonald F, Netchine I, Lombardi P, Soellner L, Begemann M, Prawitt D, Maher ER, Mannens M, Riccio A, Weksberg R, Lapunzina P, Grønskov K, Mackay DJ, Eggermann T.
EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver-Russell and Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2016 Oct;24(10):1377-87. doi: 10.1038/ejhg.2016.45. Epub 2016 May 11. PMID: 27165005; PMCID: PMC5027690.
- Eggermann T, Brioude F, Russo S, Lombardi MP, Bliek J, Maher ER, Larizza L, Prawitt D, Netchine I, Gonzales M, Grønskov K, Tümer Z, Monk D, Mannens M, Chrzanowska K, Walasek MK, Begemann M, Soellner L, Eggermann K, Tenorio J, Nevado J, Moore GE, Mackay DJ, Temple K, Gillessen-Kaesbach G, Ogata T, Weksberg R, Algar E, Lapunzina P.
Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling. Eur J Hum Genet. 2016 Jun;24(6):784-93. doi: 10.1038/ejhg.2015.224. Epub 2015 Oct 28. PMID: 26508573; PMCID: PMC4867462.
- Bak M, Boonen SE, Dahl C, Hahnemann JM, Mackay DJ, Tümer Z, Grønskov K, Temple IK, Guldberg P, Tommerup N.
Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57. BMC Med Genet. 2016 Apr 14;17:29. doi: 10.1186/s12881-016-0292-4. PMID: 27075368; PMCID: PMC4831126.
- Gede LB, Hahnemann JM, Tümer Z, Brøndum-Nielsen K, Grønskov K.
Feasibility study on the use of methylation-specific MLPA for the 11p15 region on prenatal samples.
Prenat Diagn. 2016 Jan;36(1):100-3. doi: 10.1002/pd.4752. Epub 2015 Dec 13. PMID: 26590364.
- Eggermann T, Perez de Nanclares G, Maher ER, Temple IK, Tümer Z, Monk D, Mackay DJ, Grønskov K, Riccio A, Linglart A, Netchine I.
Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci. Clin Epigenetics. 2015 Nov 14;7:123. doi: 10.1186/s13148-015-0143-8. Erratum in: Clin Epigenetics. 2016;8:27. PMID:26583054; PMCID: PMC4650860.
- Eggermann T, Netchine I, Temple IK, Tümer Z, Monk D, Mackay D, Grønskov K, Riccio A, Linglart A, Maher ER.
Congenital imprinting disorders: EUCID.net – a network to decipher their aetiology and to improve the diagnostic and clinical care. Clin Epigenetics. 2015 Mar 14;7(1):23. doi: 10.1186/s13148-015-0050-z. PMID: 25784961; PMCID: PMC4362648.
- Boonen SE, Mackay DJ, Hahnemann JM, Docherty L, Grønskov K, Lehmann A, Larsen LG, Haemers AP, Kockaerts Y, Dooms L, Vu DC, Ngoc CT, Nguyen PB, Kordonouri O, Sundberg F, Dayanikli P, Puthi V, Acerini C, Massoud AF, Tümer Z, Temple IK.
Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. Diabetes Care. 2013 Mar;36(3):505-12. doi: 10.2337/dc12-0700. Epub 2012 Nov 12. PMID: 23150280; PMCID: PMC3579357.
- Boonen SE, Hahnemann JM, Mackay D, Tommerup N, Brøndum-Nielsen K, Tümer Z, Grønskov K.
No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of Beckwith-Wiedemann Syndrome. Eur J Hum Genet. 2012 Jan;20(1):119-21. doi: 10.1038/ejhg.2011.140. Epub 2011 Aug 24. PMID: 21863059; PMCID: PMC3234508.
- Grønskov K, Poole RL, Hahnemann JM, Thomson J, Tümer Z, Brøndum-Nielsen K, Murphy R, Ravn K, Melchior L, Dedic A, Dolmer B, Temple IK, Boonen SE, Mackay DJ.
Deletions and rearrangements of the H19/IGF2 enhancer region in patients with Silver-Russell syndrome and growth retardation. J Med Genet. 2011 May;48(5):308-11. doi: 10.1136/jmg.2010.086504. Epub 2011 Jan 28. PMID: 21278389.