{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:16:02Z","timestamp":1791141362109,"version":"4.1.0"},"reference-count":38,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":3122,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because it has impact on the phenotype and recurrence risk for families. We have determined the genotype, phenotype, and epigenotype of the first 10 families to alert health professionals to this newly described genetic subgroup of diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>The 10 families (14 homozygous\/compound heterozygous individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic testing. ZFP57 was sequenced in probands and their relatives, and the methylation levels at multiple maternally and paternally imprinted loci were determined. Medical and family histories were obtained, and clinical examination was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The key clinical features in probands were transient neonatal diabetes, intrauterine growth retardation, macroglossia, heart defects, and developmental delay. However, the finding of two homozygous relatives without diabetes and normal intelligence showed that the phenotype could be very variable. The epigenotype always included total loss of methylation at the TNDM1 locus and reproducible combinations of differential hypomethylation at other maternally imprinted loci, including tissue mosaicism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>There is yet no clear genotype\u2013epigenotype\u2013phenotype correlation to explain the variable clinical presentation, and this results in difficulties predicting the prognosis of affected individuals. However, many cases have a more severe phenotype than seen in other causes of TNDM1. Further cases and global epigenetic testing are needed to clarify this.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc12-0700","type":"journal-article","created":{"date-parts":[[2012,11,14]],"date-time":"2012-11-14T01:25:54Z","timestamp":1352856354000},"page":"505-512","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":58,"title":["Transient Neonatal Diabetes, <i>ZFP57<\/i>, and Hypomethylation of Multiple Imprinted Loci"],"prefix":"10.2337","volume":"36","author":[{"given":"Susanne E.","family":"Boonen","sequence":"first","affiliation":[{"name":"Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark"},{"name":"The Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J.G.","family":"Mackay","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory, Salisbury Health Care Trust, Salisbury, U.K."},{"name":"Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne M.D.","family":"Hahnemann","sequence":"additional","affiliation":[{"name":"Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Docherty","sequence":"additional","affiliation":[{"name":"Wessex Regional Genetics Laboratory, Salisbury Health Care Trust, Salisbury, U.K."},{"name":"Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gr\u00f8nskov","sequence":"additional","affiliation":[{"name":"Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise G.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, N\u00e6stved Hospital, N\u00e6stved, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas P.","family":"Haemers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Endocrinology, Maria Hospital Noord Limburg, Overpelt, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Kockaerts","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, Campus Andr\u00e9 Dumont, Genk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutgarde","family":"Dooms","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Liege, Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u0169ng Ch\u00ed","family":"V\u0169","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Metabolism and Endocrinology, National Hospital of Paediatrics, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.T. Bich","family":"Ngoc","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Metabolism and Endocrinology, National Hospital of Paediatrics, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Bich","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Austin Health\/Northern Health, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kordonouri","sequence":"additional","affiliation":[{"name":"Diabetes Centre for Children and Adolescents, Children\u2019s Hospital at the Bult, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Sundberg","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Queen Silvia Children\u2019s Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Dayanikli","sequence":"additional","affiliation":[{"name":"American Hospital, Nisantasi, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijith","family":"Puthi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Peterborough and Stamford Hospitals Foundation Trust, Cambridgeshire, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Acerini","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Addenbrooke\u2019s Hospital, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"Massoud","sequence":"additional","affiliation":[{"name":"Children\u2019s Services, Northwick Park Hospital, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"T\u00fcmer","sequence":"additional","affiliation":[{"name":"Center for Applied Human Molecular Genetics, The Kennedy Center, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Karen","family":"Temple","sequence":"additional","affiliation":[{"name":"Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, U.K."},{"name":"Wessex Clinical Genetics Service, University Hospital Southampton NHS Trust, Southampton, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,2,13]]},"reference":[{"key":"2022031302050321200_B1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00439-005-0127-4","article-title":"Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus","volume":"119","author":"Mackay","year":"2006","journal-title":"Hum Genet"},{"key":"2022031302050321200_B2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s00439-006-0205-2","article-title":"A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus","volume":"120","author":"Mackay","year":"2006","journal-title":"Hum Genet"},{"key":"2022031302050321200_B3","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/sj.ejhg.5201993","article-title":"Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings","volume":"16","author":"Boonen","year":"2008","journal-title":"Eur J Hum Genet"},{"key":"2022031302050321200_B4","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/ajmg.c.30272","article-title":"Transient neonatal diabetes mellitus type 1","volume":"154C","author":"Mackay","year":"2010","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2022031302050321200_B5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ng.187","article-title":"Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57","volume":"40","author":"Mackay","year":"2008","journal-title":"Nat Genet"},{"key":"2022031302050321200_B6","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.devcel.2008.08.014","article-title":"A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints","volume":"15","author":"Li","year":"2008","journal-title":"Dev Cell"},{"key":"2022031302050321200_B7","doi-asserted-by":"crossref","first-page":"6900","DOI":"10.1016\/S0021-9258(17)37460-4","article-title":"A novel nuclear protein with zinc fingers down-regulated during early mammalian cell differentiation","volume":"269","author":"Okazaki","year":"1994","journal-title":"J Biol Chem"},{"key":"2022031302050321200_B8","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ydbio.2003.09.041","article-title":"Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons","volume":"265","author":"Ahn","year":"2004","journal-title":"Dev Biol"},{"key":"2022031302050321200_B9","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1471-2121-8-37","article-title":"Identifying genes preferentially expressed in undifferentiated embryonic stem cells","volume":"8","author":"Li","year":"2007","journal-title":"BMC Cell Biol"},{"key":"2022031302050321200_B10","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.molcel.2011.08.032","article-title":"In embryonic stem cells, ZFP57\/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions","volume":"44","author":"Quenneville","year":"2011","journal-title":"Mol Cell"},{"key":"2022031302050321200_B11","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1074\/jbc.M111.322644","article-title":"Zinc finger protein ZFP57 requires its co-factor to recruit DNA methyltransferases and maintains DNA methylation imprint in embryonic stem cells via its transcriptional repression domain","volume":"287","author":"Zuo","year":"2012","journal-title":"J Biol Chem"},{"key":"2022031302050321200_B12","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1136\/jmg.2006.042135","article-title":"The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region","volume":"43","author":"Rossignol","year":"2006","journal-title":"J Med Genet"},{"key":"2022031302050321200_B13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/ejhg.2008.233","article-title":"Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome","volume":"17","author":"Bliek","year":"2009","journal-title":"Eur J Hum Genet"},{"key":"2022031302050321200_B14","doi-asserted-by":"crossref","first-page":"4724","DOI":"10.1093\/hmg\/ddp435","article-title":"Multilocus methylation analysis in a large cohort of 11p15-related foetal growth disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous loss of methylation at paternal and maternal imprinted loci","volume":"18","author":"Azzi","year":"2009","journal-title":"Hum Mol Genet"},{"key":"2022031302050321200_B15","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/humrep\/den406","article-title":"Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies","volume":"24","author":"Lim","year":"2009","journal-title":"Hum Reprod"},{"key":"2022031302050321200_B16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ejhg.2009.246","article-title":"Methylation analysis of 79 patients with growth restriction reveals novel patterns of methylation change at imprinted loci","volume":"18","author":"Turner","year":"2010","journal-title":"Eur J Hum Genet"},{"key":"2022031302050321200_B17","doi-asserted-by":"crossref","first-page":"e1000423","DOI":"10.1371\/journal.pgen.1000423","article-title":"Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome)","volume":"5","author":"Meyer","year":"2009","journal-title":"PLoS Genet"},{"key":"2022031302050321200_B18","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ejhg.2011.140","article-title":"No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of Beckwith-Wiedemann Syndrome","volume":"20","author":"Boonen","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"2022031302050321200_B19","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ejmg.2009.07.005","article-title":"Screening for genomic variants in ZFP57 in Silver-Russell syndrome patients with 11p15 epimutations","volume":"52","author":"Spengler","year":"2009","journal-title":"Eur J Med Genet"},{"key":"2022031302050321200_B20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00439-004-1236-1","article-title":"Bisulphite sequencing of the transient neonatal diabetes mellitus DMR facilitates a novel diagnostic test but reveals no methylation anomalies in patients of unknown aetiology","volume":"116","author":"Mackay","year":"2005","journal-title":"Hum Genet"},{"key":"2022031302050321200_B21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N","article-title":"Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion","volume":"15","author":"den Dunnen","year":"2000","journal-title":"Hum Mutat"},{"key":"2022031302050321200_B22","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.2337\/diabetes.49.8.1359","article-title":"Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes","volume":"49","author":"Temple","year":"2000","journal-title":"Diabetes"},{"key":"2022031302050321200_B23","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.2337\/diacare.27.10.2405","article-title":"Beta-cell dysfunction in classic transient neonatal diabetes is characterized by impaired insulin response to glucose but normal response to glucagon","volume":"27","author":"Valerio","year":"2004","journal-title":"Diabetes Care"},{"key":"2022031302050321200_B24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1136\/jmg.34.1.77","article-title":"Fortuitous detection of uniparental isodisomy of chromosome 6","volume":"34","author":"Bittencourt","year":"1997","journal-title":"J Med Genet"},{"key":"2022031302050321200_B25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1399-0004.2010.01514.x","article-title":"Silver-Russell patients showing a broad range of ICR1 and ICR2 hypomethylation in different tissues","volume":"80","author":"Begemann","year":"2011","journal-title":"Clin Genet"},{"key":"2022031302050321200_B26","doi-asserted-by":"crossref","first-page":"373","DOI":"10.4161\/epi.5.5.11851","article-title":"Lessons from imprinted multilocus loss of methylation in human syndromes: A step toward understanding the mechanisms underlying these complex diseases","volume":"5","author":"Azzi","year":"2010","journal-title":"Epigenetics"},{"key":"2022031302050321200_B27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/ajmg.c.30274","article-title":"Russell-Silver syndrome","volume":"154C","author":"Eggermann","year":"2010","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2022031302050321200_B28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/2464","article-title":"Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest","volume":"20","author":"Lefebvre","year":"1998","journal-title":"Nat Genet"},{"key":"2022031302050321200_B29","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/ajmg.c.30267","article-title":"Beckwith-Wiedemann syndrome","volume":"154C","author":"Choufani","year":"2010","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2022031302050321200_B30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/ajmg.c.30271","article-title":"Imprinting on chromosome 20: tissue-specific imprinting and imprinting mutations in the GNAS locus","volume":"154C","author":"Kelsey","year":"2010","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2022031302050321200_B31","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/ng1740","article-title":"Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans","volume":"38","author":"Murdoch","year":"2006","journal-title":"Nat Genet"},{"key":"2022031302050321200_B32","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/molehr\/gaq028","article-title":"Extending the maternal-zygotic effect with genomic imprinting","volume":"16","author":"Li","year":"2010","journal-title":"Mol Hum Reprod"},{"key":"2022031302050321200_B33","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1750-1172-2-12","article-title":"Neonatal diabetes mellitus: a disease linked to multiple mechanisms","volume":"2","author":"Polak","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"2022031302050321200_B34","first-page":"7","article-title":"Neonatal diabetes: new insights into aetiology and implications","volume":"53","author":"Shield","year":"2000","journal-title":"Horm Res"},{"key":"2022031302050321200_B35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1399-5448.2009.00530.x","article-title":"Incidence of neonatal diabetes in Austria-calculation based on the Austrian Diabetes Register","volume":"11","author":"Wiedemann","year":"2010","journal-title":"Pediatr Diabetes"},{"key":"2022031302050321200_B36","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00592-011-0331-8","article-title":"Minimal incidence of neonatal\/infancy onset diabetes in Italy is 1:90,000 live births","volume":"49","author":"Iafusco","year":"2012","journal-title":"Acta Diabetol"},{"key":"2022031302050321200_B37","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.2337\/db07-0043","article-title":"Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood","volume":"56","author":"Flanagan","year":"2007","journal-title":"Diabetes"},{"key":"2022031302050321200_B38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11154-010-9150-4","article-title":"6q24 transient neonatal diabetes","volume":"11","author":"Temple","year":"2010","journal-title":"Rev Endocr Metab Disord"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/36\/3\/505\/614653\/505.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/36\/3\/505\/614653\/505.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T06:12:57Z","timestamp":1647151977000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/36\/3\/505\/38037\/Transient-Neonatal-Diabetes-ZFP57-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,13]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,2,13]]},"published-print":{"date-parts":[[2013,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc12-0700","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,13]]}}}