Syndromic Disorders Caused by Disturbed Human Imprinting

RIBERI, Evelise; CARLI, Diana; Mussa, Alessandro; FERRERO, Giovanni Battista

doi:10.4274/jcrpe.galenos.2019.2018.0249

Syndromic Disorders Caused by Disturbed Human Imprinting

Diana CARLI, (Girilmemişş)

Evelise RIBERI, (Girilmemişş)

Giovanni Battista FERRERO, (Girilmemişş)

Alessandro MUSSA (Girilmemişş)

Journal of Clinical Research in Pediatric Endocrinology

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Yıl: 2020 Cilt: 12 Sayı: 1 Sayfa Aralığı: 1 - 16 Metin Dili: İngilizce DOI: 10.4274/jcrpe.galenos.2019.2018.0249 İndeks Tarihi: 13-10-2020

Syndromic Disorders Caused by Disturbed Human Imprinting

Öz:

Imprinting disorders are a group of congenital diseases caused by dysregulation of genomic imprinting, affecting prenatal and postnatal growth, neurocognitive development, metabolism and cancer predisposition. Aberrant expression of imprinted genes can be achieved through different mechanisms, classified into epigenetic - if not involving DNA sequence change - or genetic in the case of alteredgenomic sequence. Despite the underlying mechanism, the phenotype depends on the parental allele affected and opposite phenotypes may result depending on the involvement of the maternal or the paternal chromosome. Imprinting disorders are largely underdiagnosed because of the broad range of clinical signs, the overlap of presentation among different disorders, the presence of mild phenotypes, themitigation of the phenotype with age and the limited availability of molecular techniques employed for diagnosis. This review briefly illustrates the currently known human imprinting disorders, highlighting endocrinological aspects of pediatric interest.

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1. 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, TattonBrown 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;14:229- 249. Epub 2018 Jan 29
2. 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, HokkenKoelega 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 SilverRussell syndrome: first international consensus statement. Nat Rev Endocrinol 2016;13:105-124. Epub 2016 Sep 2
3. Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Usardi A, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Freson K, García Ramirez A, Germain-Lee EL, Groussin L, Hamdy N, Hanna P, Hiort O, Jüppner H, Kamenický P, Knight N, Kottler ML, Le Norcy E, Lecumberri B, Levine MA, Mäkitie O, Martin R, Martos-Moreno GÁ, Minagawa M, Murray P, Pereda A, Pignolo R, Rejnmark L, Rodado R, Rothenbuhler A, Saraff V, Shoemaker AH, Shore EM, Silve C, Turan S, Woods P, Zillikens MC, Perez de Nanclares G, Linglart A. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol 2018;14:476-500.
4. 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;91:3-13. Epub 2016 Aug 4
5. 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;7:123.
6. 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;7:23.
7. Hanna CW, Kelsey G. The specification of imprints in mammals. Heredity (Edinb) 2014;113:176-183. Epub 2014 Jun 18
8. Robinson WP. Mechanisms leading to uniparental disomy and their clinical consequences. Bioessays 2000;22:452-459.
9. Eroglu A, Layman LC. Role of ART in imprinting disorders. Semin Reprod Med 2012;30:92-104. Epub 2012 Apr 27
10. Mussa A, Molinatto C, Cerrato F, Palumbo O, Carella M, Baldassarre G, Carli D, Peris C, Riccio A, Ferrero GB. Assisted reproductive techniques and risk of Beckwith-Wiedemann syndrome. Pediatrics 2017;20164311. Epub 2017 Jun 20
11. Temple IK, Shield JP. 6q24 transient neonatal diabetes. Rev Endocr Metab Disord 2010;11:199-204.
12. Temple IK, Mackay DJ. Diabetes Mellitus, 6q24-Related Transient Neonatal. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1534/
13. Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet 2008;40:949-951. Epub 2008 Jul 11
14. Boonen SE, Pörksen S, Mackay DJ, Oestergaard E, Olsen B, BrondumNielsen K, Temple IK, Hahnemann JM. Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. Eur J Hum Genet 2008;16:453-461. Epub 2008 Jan 16
15. Docherty LE, Poole RL, Mattocks CJ, Lehmann A, Temple IK, Mackay DJ. Further refinement of the critical minimal genetic region for the imprinting disorder 6q24 transient neonatal diabetes. Diabetologia 2010;53:2347-2351. Epub 2010 Jul 30
16. Poke G, Doody M, Prado J, Gattas M. Segmental Maternal UPD6 with Prenatal Growth Restriction. Mol Syndromol 2013;3:270-273. Epub 2012 Nov 20
17. Eggermann T, Oehl-Jaschkowitz B, Dicks S, Thomas W, Kanber D, Albrecht B, Begemann M, Kurth I, Beygo J, Buiting K. The maternal uniparental disomy of chromosome 6 (upd(6)mat) “phenotype”: result of placental trisomy 6 mosaicism? Mol Genet Genomic Med 2017;5:668-677. Epub 2017 Sep 22
18. Graham JM Jr, Zadeh N, Kelley M, Tan ES, Liew W, Tan V, Deardorff MA, Wilson GN, Sagi-Dain L, Shalev SA. KCNK9 imprinting syndromefurther delineation of a possible treatable disorder. Am J Med Genet A 2016;170:2632-2637. Epub 2016 May 6.
19. Barel O, Shalev SA, Ofir R, Cohen A, Zlotogora J, Shorer Z, Mazor G, Finer G, Khateeb S, Zilberberg N, Birk OS. Maternally Inherited Birk Barel Mental Retardation Dysmorphism Syndrome Caused by a Mutation in the Genomically Imprinted Potassium Channel KCNK9. Am J Hum Genet 2008;83:193-199.
20. Court F, Camprubi C, Garcia CV, Guillaumet-Adkins A, Sparago A, Seruggia D, Sandoval J, Esteller M, Martin-Trujillo A, Riccio A, Montoliu L, Monk D. The PEG13-DMR and brain-specific enhancers dictate imprinted expression within the 8q24 intellectual disability risk locus. Epigenetics Chromatin 2014;7:5.
21. Mussa A, Russo S, De Crescenzo A, Chiesa N, Molinatto C, Selicorni A, Richiardi L, Larizza L, Silengo MC, Riccio A, Ferrero GB. Prevalence of beckwith-wiedemann syndrome in North West of Italy. Am J Med Genet A 2013;161:2481-2486. Epub 2013 Aug 5
22. Kalish JM, Biesecker LG, Brioude F, Deardorff MA, Di Cesare-Merlone A, Druley T, Ferrero GB, Lapunzina P, Larizza L, Maas S, Macchiaiolo M, Maher ER, Maitz S, Martinez-Agosto JA, Mussa A, Robinson P, Russo S, Selicorni A, Hennekam RC. Nomenclature and definition in asymmetric regional body overgrowth. Am J Med Genet A 2017;173:1735-1738. Epub 2017 May 5
23. Mussa A, Peruzzi L, Chiesa N, De Crescenzo A, Russo S, Melis D, Tarani L, Baldassarre G, Larizza L, Riccio A, Silengo M, Ferrero GB. Nephrological findings and genotype-phenotype correlation in Beckwith-Wiedemann syndrome. Pediatr Nephrol 2012;27:397-406. Epub 2011 Oct 21
24. Shuman C, Beckwith JB, Weksberg R. Beckwith-Wiedemann Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1394/
25. Mussa A, Russo S, De Crescenzo A, Freschi A, Calzari L, Maitz S, Macchiaiolo M, Molinatto C, Baldassarre G, Mariani M, Tarani L, Bedeschi MF, Milani D, Melis D, Bartuli A, Cubellis MV, Selicorni A, Cirillo Silengo M, Larizza L, Riccio A, Ferrero GB. (Epi) genotypephenotype correlations in Beckwith-Wiedemann syndrome. Eur J Hum Genet 2016;24:183-190. Epub 2015 Apr 22
26. Brioude F, Lacoste A, Netchine I, Vazquez MP, Auber F, Audry G, Gauthier-Villars M, Brugieres L, Gicquel C, Le Bouc Y, Rossignol S. Beckwith-Wiedemann syndrome: growth pattern and tumor risk according to molecular mechanism, and guidelines for tumor surveillance. Horm Res Paediatr 2013;80:457-465. Epub 2013 Dec 4
27. Mussa A, Russo S, Larizza L, Riccio A, Ferrero GB. (Epi)genotype– phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine. Clin Genet 2016;89:403-415.
28. Ibrahim A, Kirby G, Hardy C, Dias RP, Tee L, Lim D, Berg J, MacDonald F, Nightingale P, Maher ER. Methylation analysis and diagnostics of Beckwith-Wiedemann syndrome in 1,000 subjects. Clin Epigenetics 2014;6:11.
29. Mussa A, Russo S, de Crescenzo A, Freschi A, Calzari L, Maitz S, Macchiaiolo M, Molinatto C, Baldassarre G, Mariani M, Tarani L, Bedeschi MF, Milani D, Melis D, Bartuli A, Cubellis MV, Selicorni A, Silengo MC, Larizza L, Riccio A, Ferrero GB. Fetal growth patterns in Beckwith-Wiedemann syndrome. Clin Genet 2016;90:21-27. Epub 2016 Mar 15
30. Valente FM, Sparago A, Freschi A, Hill-Harfe K, Maas SM, Frints SGM, Alders M, Pignata L, Franzese M, Angelini C, Carli D, Mussa A, Gazzin A, Gabbarini F, Acurzio B, Ferrero GB, Bliek J, Williams CA, Riccio A, Cerrato F. Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus. Genet Med 2019;21:1808-1820.
31. Rossignol S, Steunou V, Chalas C, Kerjean A, Rigolet M, ViegasPequignot E, Jouannet P, Le Bouc Y, Gicquel C. The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region. J Med Genet 2006;43:902-907. Epub 2006 Jul 6
32. Fontana L, Bedeschi MF, Maitz S, Cereda A, Faré C, Motta S, Seresini A, D’Ursi P, Orro A, Pecile V, Calvello M, Selicorni A, Lalatta F, Milani D, Sirchia SM, Miozzo M, Tabano S. Characterization of multi-locus imprinting disturbances and underlying genetic defects in patients with chromosome 11p15.5 related imprinting disorders. Epigenetics 2018;13:897-909. Epub 2018 Oct 21
33. Meyer E, Lim D, Pasha S, Tee LJ, Rahman F, Yates JR, Woods CG, Reik W, Maher ER. Germline Mutation in NLRP2 (NALP2) in a Familial Imprinting Disorder (Beckwith-Wiedemann Syndrome). PLoS Genet 2009;5:1000423.
34. Court F, Martin‐Trujillo A, Romanelli V, Garin I, Iglesias‐Platas I, Salafsky I, Guitart M, Perez de Nanclares G, Lapunzina P, Monk D. Genome‐Wide Allelic Methylation Analysis Reveals Disease‐ Specific Susceptibility to Multiple Methylation Defects in Imprinting Syndromes. Hum Mutat 2013;34:595-602. Epub 2013 Feb 19
35. Begemann M, Rezwan FI, Beygo J, Docherty LE, Kolarova J, Schroeder C, Buiting K, Chokkalingam K, Degenhardt F, Wakeling EL, Kleinle S, González Fassrainer D, Oehl-Jaschkowitz B, Turner CLS, Patalan M, Gizewska M, Binder G, Bich Ngoc CT, Chi Dung V, Mehta SG, Baynam G, Hamilton-Shield JP, Aljareh S, Lokulo-Sodipe O, Horton R, Siebert R, Elbracht M, Temple IK9, Eggermann T, Mackay DJG. Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring. J Med Genet 2018;55:497-504.
36. Tian X, Pascal G, Monget P. Evolution and functional divergence of NLRP genes in mammalian reproductive systems. BMC Evol Biol 2009;9:202.
37. Duéñez-Guzmán E, Haig D. The Evolution of Reproduction-Related NLRP Genes. J Mol Evol 2014;78:194-201. Epub 2014 Mar 11
38. Soellner L, Monk D, Rezwan FI, Begemann M, Mackay D, Eggermann T. Congenital imprinting disorders: Application of multilocus and high throughput methods to decipher new pathomechanisms and improve their management. Mol Cell Probes 2015;29:282-290. Epub 2015 Jun 10
39. Docherty LE, Rezwan FI, Poole RL, Turner CL, Kivuva E, Maher ER, Smithson SF, Hamilton-Shield JP, Patalan M, Gizewska M, Peregud-Pogorzelski J, Beygo J, Buiting K, Horsthemke B, Soellner L, Begemann M, Eggermann T, Baple E, Mansour S, Temple IK, Mackay DJ. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Nat Commun 2015;6:8086.
40. Kalish JM, Conlin LK, Bhatti TR, Dubbs HA, Harris MC, Izumi K, Mostoufi-Moab S, Mulchandani S, Saitta S, States LJ, Swarr DT, Wilkens AB, Zackai EH, Zelley K, Bartolomei MS, Nichols KE, Palladino AA, Spinner NB, Deardorff MA. Clinical features of three girls with mosaic genome‐wide paternal uniparental isodisomy. Am J Med Genet A 2013;161:1929-1939. Epub 2013 Jun 26
41. Abi Habib W, Azzi S, Brioude F, Steunou V, Thibaud N, Das Neves C, Le Jule M, Chantot-Bastaraud S, Keren B, Lyonnet S, Michot C, Rossi M, Pasquier L, Gicquel C, Rossignol S, Le Bouc Y, Netchine I. Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome. Hum Mol Genet 2014;23:5763-5773. Epub 2014 Jun 10
42. Zimmerman DL, Boddy CS, Schoenherr CS. Oct4/Sox2 Binding Sites Contribute to Maintaining Hypomethylation of the Maternal Igf2/H19 Imprinting Control Region. PLoS One 2013;8:81962.
43. Liu W, Zhang R, Wei J, Zhang H, Yu G, Li Z, Chen M, Sun X. Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays. Cytogenet Genome Res 2015;146:9-18. Epub 2015 Jul 16
44. Russo S, Calzari L, Mussa A, Mainini E, Cassina M, Di Candia S, Clementi M, Guzzetti S, Tabano S, Miozzo M, Sirchia S, Finelli P, Prontera P, Maitz S, Sorge G, Calcagno A, Maghnie M, Divizia MT, Melis D, Manfredini E, Ferrero GB, Pecile V, Larizza L. A multimethod approach to the molecular diagnosis of overt and borderline 11p15.5 defects underlying Silver-Russell and Beckwith-Wiedemann syndromes. Clin Epigenetics 2016;8:23.
45. Mussa A, Molinatto C, Baldassarre G, Riberi E, Russo S, Larizza L, Riccio A, Ferrero GB. Cancer Risk in Beckwith-Wiedemann Syndrome: A Systematic Review and Meta-Analysis Outlining a Novel (Epi) Genotype Specific Histotype Targeted Screening Protocol. J Pediatr 2016;176:142-149. Epub 2016 Jun 29
46. Maas SM, Vansenne F, Kadouch DJ, Ibrahim A, Bliek J, Hopman S, Mannens MM, Merks JH, Maher ER, Hennekam RC. Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups. Am J Med Genet A 2016;170:2248-2260. Epub 2016 Jul 15
47. Mussa A, Ferrero GB. Screening Hepatoblastoma in BeckwithWiedemann Syndrome: A Complex Issue. J Pediatr Hematol Oncol 2015;37:627.
48. Mussa A, Ferrero GB. Serum alpha-fetoprotein screening for hepatoblastoma in Beckwith-Wiedemann syndrome. Am J Med Genet A 2017;173:585-587.
49. Mussa A, Di Candia S, Russo S, Catania S, De Pellegrin M, Di Luzio L, Ferrari M, Tortora C, Meazzini MC, Brusati R, Milani D, Zampino G, Montirosso R, Riccio A, Selicorni A, Cocchi G, Ferrero GB. Recommendations of the Scientific Committee of the Italian Beckwith-Wiedemann Syndrome Association on the diagnosis, management and follow-up of the syndrome. Eur J Med Genet 2016;59:52-64. Epub 2015 Nov 22
50. Mussa A, Pagliardini S, Pagliardini V, Molinatto C, Baldassarre G, Corrias A, Silengo MC, Ferrero GB. α-Fetoprotein assay on dried blood spot for hepatoblastoma screening in children with overgrowthcancer predisposition syndromes. Pediatr Res 2014;76:544-548. Epub 2014 Aug 28
51. Mussa A, Ciuffreda VP, Sauro P, Pagliardini V, Pagliardini S, Carli D, Kalish JM8, Fagioli F9,10, Pavanello E11, Ferrero GB. Longitudinal Monitoring of Alpha-Fetoprotein by Dried Blood Spot for Hepatoblastoma Screening in Beckwith−Wiedemann Syndrome. Cancers (Basel) 2019:11.
52. Mussa A, Duffy KA, Carli D, Ferrero GB, Kalish JM. Defining an optimal time window to screen for hepatoblastoma in children with BeckwithWiedemann syndrome. Pediatr Blood Cancer 2019;66:27492. Epub 2018 Sep 30
53. Saal HM. Russell-Silver Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1324/
54. Azzi S, Salem J, Thibaud N, Chantot-Bastaraud S, Lieber E, Netchine I, Harbison MD. A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in SilverRussell syndrome. J Med Genet 2015;52:446-453. Epub 2015 May 7
55. Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Merrer ML, Burglen L, Bertrand AM, Netchine I, Bouc YL. Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet 2005;37:1003-1007. Epub 2012 Jan 16
56. Demars J, Gicquel C. Epigenetic and genetic disturbance of the imprinted 11p15 region in Beckwith-Wiedemann and Silver-Russell syndromes. Clin Genet 2012;81:350-361. Epub 2012 Jan 16
57. Begemann M, Spengler S, Gogiel M, Grasshoff U, Bonin M, Betz RC, Dufke A, Spier I, Eggermann T. Clinical significance of copy number variations in the 11p15.5 imprinting control regions: new cases and review of the literature. J Med Genet 2012;49:547-553. Epub 2012 Jul 26
58. Cytrynbaum C, Chong K, Hannig V, Choufani S, Shuman C, Steele L, Morgan T, Scherer SW, Stavropoulos DJ, Basran RK, Weksberg R. Genomic imbalance in the centromeric 11p15 imprinting center in three families: Further evidence of a role for IC2 as a cause of RussellSilver syndrome. Am J Med Genet A 2016;170:2731-2739. Epub 2016 Jul 4
59. Brioude F, Oliver-Petit I, Blaise A, Praz F, Rossignol S, Le Jule M, Thibaud N, Faussat AM, Tauber M, Le Bouc Y, Netchine I. CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell Silver syndrome. J Med Genet 2013;50:823-830. Epub 2013 Sep 24
60. Begemann M, Zirn B, Santen G, Wirthgen E, Soellner L, Büttel HM, Schweizer R, van Workum W, Binder G, Eggermann T. Paternally Inherited IGF2 Mutation and Growth Restriction. N Engl J Med 2015;373:349-356. Epub 2015 Jul 8
61. De Crescenzo A, Citro V, Freschi A, Sparago A, Palumbo O, Cubellis MV, Carella M, Castelluccio P, Cavaliere ML, Cerrato F, Riccio A. A splicing mutation of the HMGA2 gene is associated with Silver-Russell syndrome phenotype. J Hum Genet 2015;60:287-293. Epub 2015 Mar 26.
62. Leszinski GS, Warncke K, Hoefele J, Wagner M. A case report and review of the literature indicate that HMGA2 should be added as a disease gene for Silver-Russell syndrome. Gene 2018;663:110-114. Epub 2018 Apr 12
63. Abi Habib W, Brioude F, Edouard T, Bennett JT, Lienhardt-Roussie A, Tixier F, Salem J, Yuen T, Azzi S, Le Bouc Y, Harbison MD, Netchine I. Genetic disruption of the oncogenic HMGA2-PLAG1-IGF2 pathway causes fetal growth restriction. Genet Med 2018;20:250-258. Epub 2017 Aug 10
64. Eggermann T, Binder G, Brioude F, Maher ER, Lapunzina P, Cubellis MV, Bergadá I, Prawitt D, Begemann M. CDKN1C mutations: two sides of the same coin. Trends Mol Med 2014;20:614-622. Epub 2014 Sep 25
65. Bennett J, Schrier Vergano SA, Deardorff MA. IMAGe Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http:// www.ncbi.nlm.nih.gov/books/NBK190103/
66. Ioannides Y, Lokulo-Sodipe K, Mackay DJ, Davies JH, Temple IK. Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases. J Med Genet 2014;51:495-501. Epub 2014 Jun 2
67. Mitter D, Buiting K, von Eggeling F, Kuechler A, Liehr T, MauHolzmann UA, Prott EC, Wieczorek D, Gillessen-Kaesbach G. Is there a higher incidence of maternal uniparental disomy 14 [upd(14)mat]? Detection of 10 new patients by methylation‐specific PCR. Am J Med Genet A 2006;140:2039-2049.
68. Poole RL, Docherty LE, Al Sayegh A, Caliebe A, Turner C, Baple E, Wakeling E, Harrison L, Lehmann A, Temple IK, Mackay DJ; International Clinical Imprinting Consortium. Targeted methylation testing of a patient cohort broadens the epigenetic and clinical description of imprinting disorders. Am J Med Genet A 2013;161:2174- 2182. Epub 2013 Aug 2
69. Luk HM. Temple syndrome misdiagnosed as Silver-Russell syndrome. Clin Dysmorphol 2016;25:82-83.
70. Brightman DS, Lokulo-Sodipe O, Searle BA, Mackay DJG, Davies JH, Temple IK, Dauber A. Growth hormone improves short-term growth in patients with Temple Syndrome. Horm Res Paediatr 2018;90:407- 413 Epub 2019 Mar 5
71. Kagami M, Sekita Y, Nishimura G, Irie M, Kato F, Okada M, Yamamori S, Kishimoto H, Nakayama M, Tanaka Y, Matsuoka K, Takahashi T, Noguchi M, Tanaka Y, Masumoto K, Utsunomiya T, Kouzan H, Komatsu Y, Ohashi H, Kurosawa K, Kosaki K, Ferguson-Smith AC, Ishino F, Ogata T. Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes. Nat Genet 2008;40:237-242. Epub 2008 Jan 6
72. Kagami M, O’Sullivan MJ, Green AJ, Watabe Y, Arisaka O, Masawa N, Matsuoka K, Fukami M, Matsubara K, Kato F, Ferguson-Smith AC, Ogata T. The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. PLoS Genet 2010;6:e1000992.
73. Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P. Maternal uniparental disomy for chromosome 14. J Med Genet 1991;28:511- 514.
74. Briggs TA, Lokulo‐Sodipe K, Chandler KE, Mackay DJG, Temple IK. Temple syndrome as a result of isolated hypomethylation of the 14q32 imprinted DLK1/MEG3 region. Am J Med Genet A 2016;170:170-175. Epub 2015 Sep 23
75. Gillessen-Kaesbach G, Albrecht B, Eggermann T, Elbracht M, Mitter D, Morlot S, van Ravenswaaij-Arts CMA, Schulz S, Strobl-Wildemann G, Buiting K, Beygo J. Molecular and clinical studies in 8 patients with Temple syndrome. Clin Genet 2018;93:1179-1188. Epub 2018 Mar 25
76. Kagami M, Kurosawa K, Miyazaki O, Ishino F, Matsuoka K, Ogata T. Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome). Eur J Hum Genet 2015;23:1488-1498. Epub 2015 Feb 18
77. Ogata T, Kagami M. Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. J Hum Genet 2016;61:87-94. Epub 2015 Sep 17
78. Van Der Werf I, Buiting K, Czeschik C, Reyniers E, Vandeweyer G, Vanhaesebrouck P, Lüdecke HJ, Wieczorek D, Horsthemke B, Mortier G, Leroy JG, Kooy RF. Novel microdeletions on chromosome 14q32.2 suggest a potential role for non-coding RNAs in Kagami-Ogata syndrome. Eur J Hum Genet 2016;24:1724-1729. Epub 2016 Jul 13
79. Williams CA, Driscoll DJ, Dagli AI. Clinical and genetic aspects of Angelman syndrome. Genet Med 2010;12:385-395.
80. Dagli AI, Mueller J, Williams CA. Angelman Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http://www.ncbi. nlm.nih.gov/books/NBK1144/
81. Noor A, Dupuis L, Mittal K, Lionel AC, Marshall CR, Scherer SW, Stockley T, Vincent JB, Mendoza-Londono R, Stavropoulos DJ. 15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes. Hum Mutat 2015;36:689-693.
82. Meng L, Ward AJ, Chun S, Bennett CF, Beaudet AL, Rigo F. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 2015;518:409-412. Epub 2014 Dec 1
83. Brambilla P, Crinò A, Bedogni G, Bosio L, Cappa M, Corrias A, Delvecchio M, Di Candia S, Gargantini L, Grechi E, Iughetti L, Mussa A, Ragusa L, Sacco M, Salvatoni A, Chiumello G, Grugni G; Genetic Obesity Study Group of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED). Metabolic syndrome in children with Prader-Willi syndrome: The effect of obesity. Nutr Metab Cardiovasc Dis 2011;21:269-276. Epub 2010 Jan 20
84. Driscoll DJ, Miller JL, Schwartz S, Cassidy SB. Prader-Willi Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K (eds). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [cited 2019 Jan 16]. Available from: http:// www.ncbi.nlm.nih.gov/books/NBK1330/
85. Corrias A, Grugni G, Crinò A, Di Candia S, Chiabotto P, Cogliardi A, Chiumello G, De Medici C, Spera S, Gargantini L, Iughetti L, Luce A, Mariani B, Ragusa L, Salvatoni A, Andrulli S, Mussa A, Beccaria L; Study Group for Genetic Obesity of Italian Society of Pediatric Endocrinology and Diabetology (SIEDP/ISPED). Assessment of central adrenal insufficiency in children and adolescents with PraderWilli syndrome. Clin Endocrinol (Oxf) 2012;76:843-850.
86. Fountain MD Jr, Schaaf CP. MAGEL2 and Oxytocin-Implications in Prader-Willi Syndrome and Beyond. Biol Psychiatry 2015;78:78-80.
87. Meziane H, Schaller F, Bauer S, Villard C, Matarazzo V, Riet F, Guillon G, Lafitte D, Desarmenien MG, Tauber M, Muscatelli F. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism. Biol Psychiatry 2015;78:85-94. Epub 2014 Nov 20.
88. Gunay-Aygun M, Schwartz S, Heeger S, O’Riordan MA, Cassidy SB. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 2001;108:92.
89. Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 2008;40:719-721. Epub 2008 May 25
90. de Smith AJ, Purmann C, Walters RG, Ellis RJ, Holder SE, Van Haelst MM, Brady AF, Fairbrother UL, Dattani M, Keogh JM, Henning E, Yeo GS, O’Rahilly S, Froguel P, Farooqi IS, Blakemore AI. A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. Hum Mol Genet 2009;18:3257-3265. Epub 2009 Jun 4
91. Buiting K, Saitoh S, Gross S, Dittrich B, Schwartz S, Nicholls RD, Horsthemke B. Inherited microdeletions in the Angelman and PraderWilli syndromes define an imprinting centre on human chromosome 15. Nat Genet 1995;9:395-400.
92. Fontana P, Grasso M, Acquaviva F, Gennaro E, Galli ML, Falco M, Scarano F, Scarano G, Lonardo F. SNORD116 deletions cause PraderWilli syndrome with a mild phenotype and macrocephaly. Clin Genet 2017;92:440-443. Epub 2017 Mar 30
93. Rocha CF, Paiva CL. Prader-Willi-like phenotypes: a systematic review of their chromosomal abnormalities. Genet Mol Res 2014;13:2290- 2298.
94. Fountain MD, Aten E, Cho MT, Juusola J, Walkiewicz MA, Ray JW, Xia F, Yang Y, Graham BH, Bacino CA, Potocki L, van Haeringen A, Ruivenkamp CA, Mancias P, Northrup H, Kukolich MK, Weiss MM, van Ravenswaaij-Arts CM, Mathijssen IB, Levesque S, Meeks N, Rosenfeld JA, Lemke D, Hamosh A, Lewis SK, Race S, Stewart LL, Hay B, Lewis AM, Guerreiro RL, Bras JT, Martins MP, Derksen-Lubsen G, Peeters E, Stumpel C, Stegmann S, Bok LA, Santen GW, Schaaf CP. The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families. Genet Med 2017;19:45-52. Epub 2016 May 19
95. Bulcao Macedo D, Nahime Brito V, Latronico AC. New Causes of Central Precocious Puberty: The Role of Genetic Factors. Neuroendocrinology 2014;100:1-8. Epub 2014 Aug 9 96. Fuqua JS. Treatment and Outcomes of Precocious Puberty: An Update. J Clin Endocrinol Metab 2013;98:2198-2207. Epub 2013 Mar 20
97. Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN, Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi PC, Rodrigues T, Kochi C, Longui CA, Beckers D, de Zegher F, Montenegro LR, Mendonca BB, Carroll RS, Hirschhorn JN, Latronico AC, Kaiser UB. Central Precocious Puberty Caused by Mutations in the Imprinted Gene MKRN3. N Engl J Med 2013;368:2467-2475. Epub 2013 Jun 5
98. Bessa DS, Macedo DB, Brito VN, França MM, Montenegro LR, CunhaSilva M, Silveira LG, Hummel T, Bergadá I, Braslavsky D, Abreu AP, Dauber A, Mendonca BB, Kaiser UB, Latronico AC. High Frequency of MKRN3 Mutations in Male Central Precocious Puberty Previously Classified as Idiopathic. Neuroendocrinology 2017;105:17-25. Epub 2016 May 26
99. Hagen CP, Sørensen K, Mieritz MG, Johannsen TH, Almstrup K, Juul A. Circulating MKRN3 Levels Decline Prior to Pubertal Onset and Through Puberty: A Longitudinal Study of Healthy Girls. J Clin Endocrinol Metab 2015;100:1920-1926. Epub 2015 Feb 19
100. Busch AS, Hagen CP, Almstrup K, Juul A. Circulating MKRN3 Levels Decline During Puberty in Healthy Boys. J Clin Endocrinol Metab 2016;101:2588-2593. Epub 2016 Apr 8
101. Macedo DB, Abreu AP, Reis AC, Montenegro LR, Dauber A, Beneduzzi D, Cukier P, Silveira LF, Teles MG, Carroll RS, Junior GG, Filho GG, Gucev Z, Arnhold IJ, de Castro M, Moreira AC, Martinelli CE Jr, Hirschhorn JN, Mendonca BB, Brito VN, Antonini SR, Kaiser UB, Latronico AC. Central Precocious Puberty That Appears to Be Sporadic Caused by Paternally Inherited Mutations in the Imprinted Gene Makorin Ring Finger 3. J Clin Endocrinol Metab 2014;99:1097-1103. Epub 2014 Mar 14
102. Klein K, Yang J, Aisenberg J, Wright N, Kaplowitz P, Lahlou N, Linares J, Lundström E, Purcea D, Cassorla F. Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. J Pediatr Endocrinol Metab 2016;29:1241-1248.
103. Sachwitz J, Strobl-Wildemann G, Fekete G, Ambrozaitytė L, Kučinskas V, Soellner L, Begemann M, Eggermann T. Examinations of maternal uniparental disomy and epimutations for chromosomes 6, 14, 16 and 20 in Silver-Russell syndrome-like phenotypes. BMC Med Genet 2016;17:20.
104. Eggermann T, Curtis M, Zerres K, Hughes HE. Maternal uniparental disomy 16 and genetic counseling: new case and survey of published cases. Genet Couns 2004;15:183-190.
105. Scheuvens R, Begemann M, Soellner L, Meschede D, Raabe‐Meyer G, Elbracht M, Schubert R, Eggermann T. Maternal uniparental disomy of chromosome 16 [upd(16)mat]: clinical features are rather caused by (hidden) trisomy 16 mosaicism than by upd(16)mat itself. Clin Genet 2017;92:45-51. Epub 2017 Mar 8
106. Inoue T, Yagasaki H, Nishioka J, Nakamura A, Matsubara K, Narumi S, Nakabayashi K, Yamazawa K, Fuke T, Oka A, Ogata T, Fukami M, Kagami M. Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with SilverRussell syndrome phenotype of unknown aetiology. J Med Genet 2019;56:413-418. Epub 2018 Sep 21.
107. Mantovani G, Spada A. Mutations in the Gs alpha gene causing hormone resistance. Best Pract Res Clin Endocrinol Metab 2006;20:501-513.
108. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Pseudohypoparathyroidism - epidemiology, mortality and risk of complications. Clin Endocrinol (Oxf) 2016;84:904-911. Epub 2015 Oct 19
109. Elli FM, Linglart A, Garin I, de Sanctis L, Bordogna P, Grybek V, Pereda A, Giachero F, Verrua E, Hanna P, Mantovani G, Perez de Nanclares G. The Prevalence of GNAS Deficiency-Related Diseases in a Large Cohort of Patients Characterized by the EuroPHP Network. J Clin Endocrinol Metab 2016;101:3657-3668. Epub 2016 Jul 18
110. Thiele S, Mantovani G, Barlier A, Boldrin V, Bordogna P, De Sanctis L, Elli FM, Freson K, Garin I, Grybek V, Hanna P, Izzi B, Hiort O, Lecumberri B, Pereda A, Saraff V, Silve C, Turan S, Usardi A, Werner R, de Nanclares GP, Linglart A. From pseudohypoparathyroidism to inactivating PTH/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network. Eur J Endocrinol 2016;175:1-17. Epub 2016 Jul 11
111. Linglart A, Maupetit-Méhouas S, Silve C. GNAS-Related Loss-ofFunction Disorders and the Role of Imprinting. Horm Res Paediatr 2013;79:119-129. Epub 2013 Mar 29
112. Crane JL, Shamblott MJ, Axelman J, Hsu S, Levine MA, Germain‐Lee EL. Imprinting status of Galpha(s), NESP55, and XLalphas in cell cultures derived from human embryonic germ cells: GNAS imprinting in human embryonic germ cells. Clin Transl Sci 2009;2:355-360.
113. Roizen JD, Danzig J, Groleau V, McCormack S, Casella A, Harrington J, Sochett E, Tershakovec A, Zemel BS, Stallings VA, Levine MA. Resting Energy Expenditure Is Decreased in Pseudohypoparathyroidism Type 1A. J Clin Endocrinol Metab 2016;101:880-888. Epub 2015 Dec 28
114. Simpson C, Grove E, Houston BA. Pseudopseudohypoparathyroidism. Lancet 2015;385:1123. Epub 2014 Dec 5
115. Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS ‐based heterotopic ossification. Am J Med Genet A 2008;146:1788-1796.
116. Zazo C, Thiele S, Martín C, Fernandez-Rebollo E, Martinez-Indart L, Werner R, Garin I; Spanish PHP Group, Hiort O, Perez de Nanclares G. Gsα activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus. J Bone Miner Res 2011;26:1864-1870.
117. Mariot V, Maupetit-Méhouas S, Sinding C, Kottler ML, Linglart A. A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance. J Clin Endocrinol Metab 2008;93:661-665. Epub 2008 Jan 8
118. Jüppner H, Linglart A, Fröhlich LF, Bastepe M. Autosomaldominant pseudohypoparathyroidism type Ib is caused by different microdeletions within or upstream of the GNAS locus. Ann N Y Acad Sci 2006;1068:250-255.
119. Perez-Nanclares G, Velayos T, Vela A, Muñoz-Torres M, Castaño L. Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus. PLoS ONE 2015;10:e0117691.
120. Mulchandani S, Bhoj EJ, Luo M, Powell-Hamilton N, Jenny K, Gripp KW, Elbracht M, Eggermann T, Turner CL, Temple IK, Mackay DJ, Dubbs H, Stevenson DA, Slattery L, Zackai EH, Spinner NB, Krantz ID, Conlin LK. Maternal uniparental disomy of chromosome 20: a novel imprinting disorder of growth failure. Genet Med 2015;18:309- 315. Epub 2015 Aug 6

APA	CARLI D, RIBERI E, FERRERO G, Mussa A (2020). Syndromic Disorders Caused by Disturbed Human Imprinting. , 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
Chicago	CARLI Diana,RIBERI Evelise,FERRERO Giovanni Battista,Mussa Alessandro Syndromic Disorders Caused by Disturbed Human Imprinting. (2020): 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
MLA	CARLI Diana,RIBERI Evelise,FERRERO Giovanni Battista,Mussa Alessandro Syndromic Disorders Caused by Disturbed Human Imprinting. , 2020, ss.1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
AMA	CARLI D,RIBERI E,FERRERO G,Mussa A Syndromic Disorders Caused by Disturbed Human Imprinting. . 2020; 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
Vancouver	CARLI D,RIBERI E,FERRERO G,Mussa A Syndromic Disorders Caused by Disturbed Human Imprinting. . 2020; 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
IEEE	CARLI D,RIBERI E,FERRERO G,Mussa A "Syndromic Disorders Caused by Disturbed Human Imprinting." , ss.1 - 16, 2020. 10.4274/jcrpe.galenos.2019.2018.0249
ISNAD	CARLI, Diana vd. "Syndromic Disorders Caused by Disturbed Human Imprinting". (2020), 1-16. https://doi.org/10.4274/jcrpe.galenos.2019.2018.0249

APA	CARLI D, RIBERI E, FERRERO G, Mussa A (2020). Syndromic Disorders Caused by Disturbed Human Imprinting. Journal of Clinical Research in Pediatric Endocrinology, 12(1), 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
Chicago	CARLI Diana,RIBERI Evelise,FERRERO Giovanni Battista,Mussa Alessandro Syndromic Disorders Caused by Disturbed Human Imprinting. Journal of Clinical Research in Pediatric Endocrinology 12, no.1 (2020): 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
MLA	CARLI Diana,RIBERI Evelise,FERRERO Giovanni Battista,Mussa Alessandro Syndromic Disorders Caused by Disturbed Human Imprinting. Journal of Clinical Research in Pediatric Endocrinology, vol.12, no.1, 2020, ss.1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
AMA	CARLI D,RIBERI E,FERRERO G,Mussa A Syndromic Disorders Caused by Disturbed Human Imprinting. Journal of Clinical Research in Pediatric Endocrinology. 2020; 12(1): 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
Vancouver	CARLI D,RIBERI E,FERRERO G,Mussa A Syndromic Disorders Caused by Disturbed Human Imprinting. Journal of Clinical Research in Pediatric Endocrinology. 2020; 12(1): 1 - 16. 10.4274/jcrpe.galenos.2019.2018.0249
IEEE	CARLI D,RIBERI E,FERRERO G,Mussa A "Syndromic Disorders Caused by Disturbed Human Imprinting." Journal of Clinical Research in Pediatric Endocrinology, 12, ss.1 - 16, 2020. 10.4274/jcrpe.galenos.2019.2018.0249
ISNAD	CARLI, Diana vd. "Syndromic Disorders Caused by Disturbed Human Imprinting". Journal of Clinical Research in Pediatric Endocrinology 12/1 (2020), 1-16. https://doi.org/10.4274/jcrpe.galenos.2019.2018.0249