Human imprinting syndromes

Epigenomics

Volumn 1, Issue 2, 2009, Pages 347-369

  Lim, Derek H K ^a,b   Maher, Eamonn R ^a,b  

^a BIRMINGHAM WOMEN S HOSPITAL   (United Kingdom)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Beckwith Wiedemann syndrome; Genomic imprinting; Hydatidiform mole; NLRP; Prader Willi Angelman syndrome; Pseudohypoparathyroidism; Silver Russell syndrome; Transient neonatal diabetes; Uniparental disomy

Indexed keywords

NLRP7 PROTEIN, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ALBRIGHT SYNDROME; BECKWITH WIEDEMANN SYNDROME; CHROMOSOME 11; CHROMOSOME 14; CHROMOSOME 15; CHROMOSOME 20; CHROMOSOME 6; CHROMOSOME DISORDER; DIABETES MELLITUS; FEMALE; GENETICS; GENOME IMPRINTING; HAPPY PUPPET SYNDROME; HUMAN; HYDATIDIFORM MOLE; MULTIGENE FAMILY; MUTATION; PATHOLOGY; PHYSIOLOGY; PRADER WILLI SYNDROME; PREGNANCY; PSEUDOHYPOPARATHYROIDISM; REVIEW; SILVER RUSSELL SYNDROME; UNIPARENTAL DISOMY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANGELMAN SYNDROME; BECKWITH-WIEDEMANN SYNDROME; CHROMOSOME DISORDERS; CHROMOSOMES, HUMAN, PAIR 11; CHROMOSOMES, HUMAN, PAIR 14; CHROMOSOMES, HUMAN, PAIR 15; CHROMOSOMES, HUMAN, PAIR 20; CHROMOSOMES, HUMAN, PAIR 6; DIABETES MELLITUS; FEMALE; FIBROUS DYSPLASIA, POLYOSTOTIC; GENOMIC IMPRINTING; HUMANS; HYDATIDIFORM MOLE; MULTIGENE FAMILY; MUTATION; PRADER-WILLI SYNDROME; PREGNANCY; PSEUDOHYPOPARATHYROIDISM; SILVER-RUSSELL SYNDROME; UNIPARENTAL DISOMY;

EID: 84859726550     PISSN: 17501911     EISSN: 1750192X     Source Type: Journal    
DOI: 10.2217/EPI.09.24     Document Type: Review

References (188)

1. Reik W, Walter J: Genomic imprinting: parental influence on the genome. Nat. Rev. Genet. 2, 21-32 (2001).
2. McGrath J, Solter D: Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179-183(1984).
3. Surani MA, Barton SC, Norris ML: Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308, 548-550 (1984).
4. Kajii T, Ohama K: Androgenetic origin of hydatidiform mole. Nature 268, 633-634 (1977).
5. Ohama K, Kajii T, Olcamoto E et al.: Dispermic origin of XY hydatidiform moles. Nature 292, 551-552(1981).
6. Ohama K, Nomura K, Okamoto E, Fukuda Y, Ihara T, Fujiwara A: Origin of immature teratoma of the ovary. Am. J. Obstet. Gynecol. 152, 896-900 (1985).
7. Cattanach BM, Kirk M: Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315, 496-498 (1985).
8. Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N: The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349, 84-87 (1991).
9. Neumann B, Kubicka P, Barlow DP: Characteristics of imprinted genes. Nat. Genet. 9, 12-13(1995).
10. Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33(Suppl.), 245-254 (2003).
11. Dennis C: Epigenetics and disease: altered states. Nature 421, 686-688 (2003).
12. Horike S, Mitsuya K, Meguro M et al.: Targeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome. Hum. Mol. Genet. 9, 2075-2083 (2000).
13. Bell AC, Felsenfeld G: Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405, 482-485 (2000).
14. Lee J, Inoue K, Ono R et al.: Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Development 129, 1807-1817 (2002).
15. Szabo PE, Hubner K, Scholer H, Mann JR.: Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mec. Dev. 115, 157-160 (2002).
16. Cooper WN, Luharia A, Evans GA et al.: Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. Eur. J. Hum. Genet. 13, 1025-1032 (2005).
17. Abu-Amero S, Monk D, Frost J, Preece M, Stanier P, Moore GE: The genetic aetiology of Silver-Russell syndrome. J. Med. Genet. 45, 193-199 (2008).
18. Jirtle RL, Skinner MK: Environmental epigenomics and disease susceptibility. Nat. Rev. Genet. 8, 253-262 (2007).
19. Coan PM, Burton GJ, Ferguson-Smith AC: Imprinted genes in the placenta - a review. Placenta 26(Suppl. A), S10-S20 (2005).
20. Davies W, Isles AR, Wilkinson LS: Imprinted gene expression in the brain. Neurosci. Biobehav. Rev. 29, 421-430 (2005).
21. Hensen EF, Jordanova ES, van Minderhout IJ et al.: Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene 23, 4076-4083 (2004).
22. Bartolomei MS, Zemel S, Tilghman SM: Parental imprinting of the mouse H19 gene. Nature 351, 153-155(1991).
23. DeChiara TM, Robertson EJ, Efstratiadis A: Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849-859 (1991).
24. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM: CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405, 486-489 (2000).
25. Maher ER, Reik W: Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J. Clin. Invest. 105, 247-252 (2000).
26. Wan LB, Bartolomei MS: Regulation of imprinting in clusters: noncoding RNAs versus insulators. Adv. Genet. 61, 207-223 (2008).
27. Smilinich NJ, Day CD, Fitzpatrick GV et al: A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proc. Natl Acad. Sci. USA 96, 8064-8069 (1999).
28. Diaz-Meyer N, Day CD, Khatod K et al.: Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J. Med. Genet. 40, 797-801 (2003).
29. Lee MP, DeBaun MR, Mitsuya K et al.: Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. Proc. Natl Acad. Sci. USA 96, 5203-5208 (1999).
30. Weksberg R, Shuman C, Beckwith J B: Beckwith-Wiedemann syndrome. Eur. J. Hum. Genet. (2009) (Epub ahead of print).
31. Smith AC, Choufani S, Ferreira JC, Weksberg R: Growth regulation, imprinted genes, and chromosome 11p15.5. Pediatr. Res. 61, R43-R47 (2007).
32. Haig D: Genomic imprinting and kinship: how good is the evidence? Annu. Rev. Genet. 38, 553-585 (2004).
33. Reik W, Maher ER: Imprinting in clusters: lessons from Beckwith-Wiedemann syndrome. Trends Genet. 13, 330-334 (1997).
34. Slavotinek A, Gaunt L, Donnai D: Paternally inherited duplications of Up15.5 and Beckwith-Wiedemann syndrome. J. Med. Genet. 34, 819-826(1997).
35. Elliott M, Bayly R, Cole T, Temple IK, Maher ER: Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases. Clin. Genet. 46, 168-174 (1994).
36. Elliott M, Maher ER: Beckwith-Wiedemann syndrome. J. Med. Genet. 31, 560-564 (1994).
37. Everman DB, Shuman C, Dzolganovski B, O'Riordan MA, Weksberg R, Robin NH: Serum a-fetoprotein levels in Beckwith-Wiedemann syndrome. J. Pediatr. 137, 123-127(2000).
38. Beckwith JB: Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations. Am. J. Med. Genet. 79, 268-273 (1998).
39. Scott RH, Walker L, Olsen OE et al.: Surveillance for Wilms tumor in at-risk children: pragmatic recommendations for best practice. Arch. Dis. Child. 91, 995-999 (2006).
40. Niemitz EL, DeBaun MR, Fallon J et al.: Microdeletion of LIT1 in familial Beckwith-Wiedemann syndrome. Am. J. Hum. Genet. 75, 844-849 (2004).
41. Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC, Riccio A: Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat. Genet. 36, 958-960 (2004).
42. Sparago A, Russo S, Cerrato F et al.: Mechanisms causing imprinting defects in familial Beckwith-Wiedemann syndrome with Wilms' tumor. Hum. Mol. Genet. 16, 254-264 (2007).
43. Scott RH, Douglas J, Baskcomb L et al.: Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation. J. Med. Genet. 45, 106-113 (2008).
44. Hatada I, Ohashi H, Fukushima Y et al.: An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. Nat. Genet. 14, 171-173 (1996).
45. Lam WW, Hatada I, Ohishi S et al.: Analysis of germline CDKN1C (p57K1P2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype cotrelation. J. Med. Genet. 36, 518-523 (1999).
46. Meyer E, Lim D, Pasha S et al.: Germline mutation in NLRP2 (NALP2) in a familial imprinting disorder (Beckwith-Wiedemann Syndrome). PLoS Genet. 5, E1000423 (2009).
47. Scott RH, Douglas J, Baskcomb L et al.: Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat. Genet. 40, 1329-1334 (2008).
48. Maher ER, Brueton LA, Bowdin SC et al.: Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). J. Med. Genet. 40, 62-64 (2003).
49. DeBaun MR, Niemitz EL, Feinberg AP: Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am. J. Hum. Genet. 72, 156-160 (2003).
50. Gicquel C, Gaston V, Mandelbaum J, Siffroi JP, Flahault A, Le Bouc Y: In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCNIOT gene. Am. J. Hum. Genet. 72, 1338-1341 (2003).
51. Halliday J, Oke K, Breheny S, Algar E, J Amor D: Beckwith-Wiedemann syndrome and IVF: a case-control study. Am. J. Hum. Genet. 75, 526-528 (2004).
52. Rossignol S, Steunou V, Chalas C et al.: 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. 43, 902-907 (2006).
53. Lim D, Bowdin SC, Tee L et al.: Clinical and molecular genetic features of Beckwith-Wiedemann syndrome associated with assisted reproductive technologies. Hum. Reprod. 24, 741-747 (2009).
54. Bliek J, Verde G, Callaway J et al.: Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome. Eur. J. Hum. Genet. 17, 611-619(2009).
55. Amor DJ, Halliday J: A review of known imprinting syndromes and their association with assisted reproduction technologies. Hum. Reprod. 23, 2826-2834 (2008).
56. Manipalviratn S, DeCherney A, Segars J: Imprinting disorders and assisted reproductive technology. Fertil. Steril. 91, 305-315 (2009).
57. Silver HK, Kiyasu W, George J, Deamer WC: Syndrome of congenital hemihypertrophy, shortness of stature, and elevated urinary gonadotropins. Pediatrics 12, 368-376 (1953).
58. Russell A: A syndrome of intra-uterine dwarfism recognizable at birth with cranio-facial dysostosis, disproportionately short arms, and other anomalies (5 examples). Proc. R. Soc. Med. 47, 1040-1044 (1954).
59. Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC: The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria. J. Med. Genet. 36, 837-842 (1999).
60. Tomiyama H, Ibuki T, Nakajima Y, Tanaka Y: Late intraoperative hypoglycemia in a patient with Russell-Silver syndrome. J. Clin. Anesth. 11, 80-82 (1999).
61. Stanhope R, Albanese A, Azcona C: Growth hormone treatment of Russell-Silver syndrome. Horm. Res. 49(Suppl. 2), 37-40 (1998).
62. Anderson J, Viskochil D, O'Gorman M, Gonzales C: Gastrointestinal complications of Russell-Silver syndrome: a pilot study. Am. J. Med. Genet. 113. 15-19 (2002).
63. Duncan PA, Hall JG, Shapiro LR, Vibert BK: Three-generation dominant transmission of the Silver-Russell syndrome. Am. J. Med. Genet. 35, 245-250(1990).
64. Rossignol S, Netchine I, Le Bouc Y, Gicquel C: Epigenetics in Silver-Russell syndrome. Best Pract. Res. Clin. Endocrinol. Metab. 22, 403-414(2008).
65. Gicquel C, Rossignol S, Cabrol S et al.: Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat. Genet. 37, 1003-1007 (2005).
66. Netchine I, Rossignol S, Dufourg MN et al.: 11p15 imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations. J. Clin. Endocrinol. Metab. 92, 3148-3154 (2007).
67. Schonherr N, Meyer E, Roos A, Schmidt A, Wollmann HA, Eggermann T: The centromeric 11p15 imprinting centre is also involved in Silver-Russell syndrome. J. Med. Genet. 44, 59-63 (2007).
68. Eggermann T, Schonherr N, Meyer E et al.: Epigenetic mutations in 11p15 in Silver-Russell syndrome are restricted to the telomeric imprinting domain. J. Med. Genet. 43, 615-616(2006).
69. Binder G, Seidel AK, Weber K et al.: 1GF-I1 serum levels are normal in children with Silver-Russell syndrome who frequently carry epimutations at the IGF2 locus. J. Clin. Endocrinol. Metab. 91, 4709-4712 (2006).
70. Bullman H, Lever M, Robinson DO, Mackay DJ, Holder SE, Wakeling EL: Mosaic maternal uniparental disomy of chromosome 11 in a patient with Silver-Russell syndrome. J. Med. Genet. 45, 396-399 (2008).
71. Hannula K, Kere J, Pirinen S, Holmberg C, Lipsanen-Nyman M: Do patients with maternal uniparental disomy for chromosome 7 have a distinct mild Silver-Russell phenotype? J. Med. Genet. 38, 273-278 (2001).
72. van Haelst MM, Eussen HJ, Visscher F et al.: Silver-Russell phenotype in a patient with pure trisomy 1q32.1-q42.1: further delineation of the pure 1q trisomy syndrome. J. Med. Genet. 39, 582-585 (2002).
73. Kennerknecht I, Barbi G, Rodens K: Dup(1q) (q42 - >qter) syndrome: case report and review of literature. Am. J. Med. Genet. 47, 1157-1160(1993).
74. Ramirez-Duenas ML, Medina C, Ocampo-Campos R, Rivera H: Severe Silver-Russell syndrome and translocation (17;20) (q25;q13). Clin. Genet. 41, 51-53 (1992).
75. Midro AT, Debek K, Sawicka A, Marcinkiewicz D, Rogowska M: Second observation of Silver-Russel syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25. Clin. Genet. 44, 53-55(1993).
76. Dorr S, Midro AT, Farber C, Giannakudis J, Hansmann I: Construction of a detailed physical and transcript map of the candidate region for Russell-Silver syndrome on chromosome 17q23-q24. Genomics 71, 174-181 (2001).
77. Eggermann T, Eggermann K, Mergenthaler S et al.: Paternally inherited deletion of CSH1 in a patient with Silver-Russell syndrome. J. Med. Genet. 35, 784-786 (1998).
78. Prager S, Wollmann HA, Mergenthaler S et al.: Characterization of genomic variants in CSHl and GH2, two candidate genes for Silver-Russell syndrome in 17q24-q25. Genet. Test. 7, 259-263 (2003).
79. Hitchins MP, S Abu-Amero, Apostolidou S et al.: Investigation of the GRB2, GRB7, and CSHl genes as candidates for the Silver-Russell syndrome (SRS) on chromosome 17q. J. Med. Genet. 39, E13 (2002).
80. Eggermann T, Schonherr N, Eggermann K, Wollmann H: Hypomethylation in the 11p15 telomeric imprinting domain in a patient with Silver-Russell syndrome with a CSHl deletion (17q24) renders a functional role of this alteration unlikely. J. Med. Genet. 44, E77 (2007).
81. Runte M, Huttenhofer A, Gross S, Kiefmann M, Horsthemke B, Buiting K: The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum. Mol. Genet. 10, 2687-2700 (2001).
82. Landers M, Bancescu DL, Le Meur E et al.: Regulation of the large (approximately 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn. Nucleic Acids Res. 32, 3480-3492 (2004).
83. Hulten M, Armstrong S, Challinor P et al.: Genomic imprinting in an Angelman and Prader-Willi translocation family. Lancet 338, 638-639(1991).
84. Williams CA, Beaudet AL, Clayton-Smith J et al.: Angelman syndrome 2005: updated consensus for diagnostic criteria. Am. J. Med. Genet. A 140, 413-418 (2006).
85. Williams CA: Neurological aspects of the Angelman syndrome. Brain Dev. 27, 88-94 (2005).
86. Butler MG, Theodoro MF, Bittel DC, Donnelly JE: Energy expenditure and physical activity in Prader-Willi syndrome: comparison with obese subjects. Am. J. Med. Genet. A 143, 449-459 (2007).
87. Cassidy SB, Driscoll DJ: Prader-Willi syndrome. Eur. J. Hum. Genet. 17, 3-13 (2009).
88. Whittington J, Holland A, Webb T, Butler J, Clarke D, Boer H: Academic underachievement by people with Prader-Willi syndrome. J. Intellect. Disabil. Res. 48, 188-200 (2004).
89. Descheemaeker MJ, Govers V, Vermeulen P, Fryns JP: Pervasive developmental disorders in Prader-Willi syndrome: the Leuven experience in 59 subjects and controls. Am. J. Med. Genet. A 140, 1136-1142 (2006).
90. Wigren M, Hansen S: ADHD symptoms and insistence on sameness in Prader-Willi syndrome. J. Intellect. Disabil. Res. 49, 449-456 (2005).
91. Steinhausen HC, Eiholzer U, Hauffa BP, Malin Z: Behavioural and emotional disturbances in people with Prader-Willi Syndrome. J. Intellect. Disabil. Res. 48, 47-52 (2004).
92. Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken-Koelega AC: Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment. J. Clin. Endocrinol. Metab. 91, 4911-4915 (2006).
93. Priano L, Grugni G, Miscio G et al.: Sleep cycling alternating pattern (CAP) expression is associated with hypersomnia and GH secretory pattern in Prader-Willi syndrome. Sleep Med. 7, 627-633 (2006).
94. Fan Z, Greenwood R, Fisher A, Pendyal S, Powell CM: Characteristics and frequency of seizure disorder in 56 patients with Prader-Willi syndrome. Am. J. Med. Genet. A 149A, 1581-1584 (2009).
95. Crino A, Schiaffini R, Ciampalini P et al.: Hypogonadism and pubertal development in Prader-Willi syndrome. Eur J. Pediatr. 162, 327-333 (2003).
96. Akefeldt A, Tornhage CJ, Gillberg C: 'A woman with Prader-Willi syndrome gives birth to a healthy baby girl'. Dev. Med. Child Neurol. 41, 789-790 (1999).
97. Schulze A, Mogensen H, Hamborg-Petersen B, Graem N, Ostergaard JR, Brondum-Nielsen K: Fertility in Prader-Willi syndrome: a case report with Angelman syndrome in the offspring. Acta Paediatr. 90, 455-459 (2001).
98. Burman P, Ritzen EM, Lindgren AC: Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr. Rev. 22, 787-799 (2001).
99. 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 108, E92 (2001).
100. Magenis RE, Toth-Fejel S, Allen LJ et al.: Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences. Am. J. Med. Genet. 35, 333-349 (1990).
101. Zori R, Williams C, Mattei JF, Moncla A: Parental origin of del(15)(q11-q13) in Angelman and Prader-Willi syndromes. Am. J. Med. Genet. 37, 294-295 (1990).
102. Knoll JH, Nicholls RD, Magenis RE, Graham JM Jr, Lalande M, Latt SA: Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am. J. Med. Genet. 32, 285-290 (1989).
103. Nicholls RD, Knoll JH, Butler MG, Karam S, Lalande M: Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome. Nature 342, 281-285 (1989).
104. Knoll JH, Glatt KA, Nicholls RD, Malcolm S, Lalande M: Chromosome 15 uniparental disomy is not frequent in Angelman syndrome. Am. J. Hum. Genet. 48, 16-21 (1991).
105. Kishino T, Lalande M, Wagstaff J: UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet. 15, 70-73 (1997).
106. Matsuura T, Sutcliffe JS, Fang P et al.: Denovo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat. Genet. 15, 74-77 (1997).
107. Sahoo T, del Gaudio D, German JR et al.: Prader-Willi phenotype caused by paternal deficiency for the HB1I-85 C/D box small nucleolar RNA cluster. Nat. Genet. 40, 719-721 (2008).
108. de Smith AJ, Purmann C, Walters RG et al.: A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism. Hum. Mol. Genet. 18, 3257-3265 (2009).
109. Gallagher RC, Pils B, Albalwi M, Francke U: Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome. Am. J. Hum. Genet. 71, 669-678 (2002).
110. Schule B, Albalwi M, Northrop E et al.: Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15)(q27;q11.2) associated with Prader-Willi syndrome. BMC Med. Genet. 6, 18 (2005).
111. Horsthemke B, Buiting K: Imprinting defects on human chromosome 15. Cytogenet. Genome Res. 113, 292-299 (2006).
112. Buiting K, Lich C, Cottrell S, Barnicoat A, Horsthemke B: A 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bp. Hum. Genet. 105, 665-666 (1999).
113. Bielinska B, Blaydes SM, Buiting K et al.: De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch. Nat. Genet. 25, 74-78 (2000).
114. Horsthemke B, Wagstaff J: Mechanisms of imprinting of the Prader-Willi/Angelman region. Am. J. Med. Genet. A 146A, 2041-2052 (2008).
115. Sahoo T, Peters SU, Madduri NS et al: Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. J. Med. Genet. 43, 512-516 (2006).
116. Lossie AC, Whitney MM, Amidon D et al.: Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J. Med. Genet. 38, 834-845 (2001).
117. Saitoh S, Wada T, Okajima M, Takano K, Sudo A, Niikawa N: Uniparental disomy and imprinting defects in Japanese patients with Angelman syndrome. Brain Dev. 27, 389-391 (2005).
118. Nazlican H, Zeschnigk M, Claussen U et al.: Somatic mosaicism in patients with Angelman syndrome and an imprinting defect. Hum. Mol. Genet. 13, 2547-2555 (2004).
119. Cox GF, Burger J, Lip V et al.: Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am. J. Hum. Genet. 71, 162-164 (2002).
120. Orstavik KH, Eiklid K, van der Hagen CB et al.: Another case of imprinting defect in a girl with Angelman syndrome who was conceived by intracytoplasmic semen injection. Am. J. Hum. Genet. 72, 218-219 (2003).
121. Ludwig M, Katalinic A, Gross S, Sutcliffe A, Varon R, Horsthemke B: Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples. J. Med. Genet. 42, 289-291 (2005).
122. Kamiya M, Judson H, Okazaki Y et al.: The cell cycle control gene ZACIPLAGL1 is imprinted - a strong candidate gene for transient neonatal diabetes. Hum. Mol. Genet. 9, 453-460 (2000).
123. Arima T, Drewell RA, Arney KL et al: A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. Hum. Mol. Genet. 10, 1475-1483 (2001).
124. Mackay DJ, Coupe AM, Shield JP, Storr JN, Temple IK, Robinson DO: Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus. Hum. Genet. 110, 139-144 (2002).
125. Gardner RJ, Mackay DJ, Mungall AJ et al.: An imprinted locus associated with transient neonatal diabetes mellitus. Hum. Mol. Genet. 9, 589-596 (2000).
126. Temple IK, Shield JP: Transient neonatal diabetes, a disorder of imprinting. J. Med. Genet. 39, 872-875 (2002).
127. Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield J P: Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes. Diabetes 49, 1359-1366 (2000).
128. Temple IK: Imprinting in human disease with special reference to transient neonatal diabetes and Beckwith-Wiedemann syndrome. Endocr. Dev. 12, 113-123 (2007).
129. Mackay DJ, Boonen SE, Clayton-Smith J et al.: A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Hum. Genet. 120, 262-269 (2006).
130. Mackay DJ, Hahnemann JM, Boonen SE et al.: Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. Hum. Genet. 119, 179-184 (2006).
131. Mackay DJ, Callaway JL, Marks SM et al.: Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat. Genet. 40, 949-951 (2008).
132. Li X, Ito M, Zhou F et al.: A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev. Cell 15, 547-557 (2008).
133. Lin SP, Voungson N, Takada S et al.: Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlkl-Gt12 imprinted cluster on mouse chromosome 12. Nat. Genet. 35, 97-102 (2003).
134. Geuns E, De Temmerman N, Hilven P, Van Steirteghem A, Liebacrs I, De Rycke M: Methylation analysis of the intergenic differentially methylated region of DLK1-GTL2 in human. Eur. J. Hum. Genet. 15, 352-361 (2007).
135. Edwards CA, Ferguson-Smith AC: Mechanisms regulating imprinted genes in clusters. Curr. Opin. Cell Biol. 19, 281-289 (2007).
136. Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P: Maternal uniparental disomy for chromosome 14. J. Med. Genet. 28, 511-514 (1991).
137. Kotzot D, Utetmann G: Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated. Am. J. Med. Genet. A 136, 287-305 (2005).
138. Mitter D, Buiting K, von Eggeling F et al.: 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 140, 2039-2049 (2006).
139. Cox H, Bullman H, Temple IK: Maternal UPD(14) in the patient with a normal karyotype: clinical report and a systematic search for cases in samples sent for testing for Prader-Willi syndrome. Am. J. Med. Genet. A 127A, 21-25(2004).
140. Kagami M, Sekita Y, Nishimura G et al.: Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes. Nat. Genet. 40, 237-242 (2008).
141. Temple IK, Shrubb V, Lever M, Bullman H, Mackay DJ: Isolated imprinting mutation of the DLK1/GTL2 locus associated with a clinical presentation of maternal uniparental disomy of chromosome 14. J. Med. Genet. 44, 637-640 (2007).
142. Kurosawa K, Sasaki H, Sato Y et al.: Paternal UPD14 is responsible for a distinctive malformation complex. Am. J. Med. Genet. 110, 268-272(2002).
143. Offiah AC, Cornette L, Hall CM: Paternal uniparental disomy 14: introducing the 'coat-hanger' sign. Pediatr. Radiol. 33, 509-512 (2003).
144. Curtis L, Antonelli E, Vial Y et al: Prenatal diagnostic indicators of paternal uniparental disomy 14. Prenat. Diagn. 26, 662-666 (2006).
145. Seitz H, Youngson N, Lin SP et al.: Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-likegene. Nat. Genet. 34, 261-262 (2003).
146. Davis E, Calment F, Tordoir X et al.: RNAi-mediated allelic trans-interaction at the imprinted Rtll/Pegll locus. Curr. Biol. 15, 743-749 (2005).
147. Sekita Y, Wagatsuma H, Nakamura K et al: Role of retrotransposon-derived imprinted gene, Rtll, in the feto-maternal interface of mouse placenta. Nat. Genet. 40, 243-248 (2008).
148. Weinstein LS, Yu S, Warner DR, Liu J: Endocrine manifestations of stimulatory G protein a-subunit mutations and the role of genomic imprinting. Endocr. Rev. 22, 675-705 (2001).
149. Peters J, Wroe SF, Wells CA et al.: A cluster of oppositely imprinted transcripts at the Gnas locus in the distal imprinting region of mouse chromosome 2. Proc. Natl Acad. Sci. USA 96, 3830-3835 (1999).
150. Liu J, Yu S, Litman D, Chen W, Weinstein LS: Identification of a methylation imprint mark within the mouse Gnas locus. Mol. Cell. Biol 20, 5808-5817 (2000).
151. Kehlenbach RH, Matthey J, Huttner WB: XL a s is a new type of G protein. Nature 372, 804-809 (1994).
152. Wroe SF, Kelsey G, Skinner JA et al.: An imprinted transcript, antisense to Nesp, adds complexity to the cluster of imprinted genes at the mouse Gnas locus. Proc. Natl Acad. Sci. USA 97, 3342-3346 (2000).
153. Yu S, Yu D, Lee E et al.: Variable and tissue-specific hormone resistance in heterotrimeric Gs protein a-subunit (Gsa) knockout mice is due to tissue-specific imprinting of the gsa gene. Proc. Natl Acad. Sci. USA 95, 8715-8720 (1998).
154. Hayward BE, Kamiya M, Strain L et al.: The human GNASJ gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc. Natl Acad. Sci. USA 95, 10038-10043 (1998).
155. Hayward BE, Moran V, Strain L, Bonthron DT: Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc. Natl Acad. Sci. USA 95, 15475-15480 (1998).
156. Williamson CM, Ball ST, Nottingham WT et al.: A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas. Nat. Genet. 36, 894-899 (2004).
157. Liu J, Nealon JG, Weinstein LS: Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB. Hum. Mol. Genet. 14, 95-102 (2005).
158. Williamson CM, Turner MD, Ball ST et al.: Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster. Nat. Genet. 38, 350-355 (2006).
159. de Nanclares GP, Fernandez-Rebollo E, Santin I et al.: Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy. J. Clin. Endocrinol. Metab. 92, 2370-2373 (2007).
160. Davies SJ, Hughes HE: Imprinting in Albright's hereditary osteodystrophy. J. Med. Genet. 30, 101-103 (1993).
161. Aldred MA, Aftimos S, Hall C et al.: Constitutional deletion of chromosome 20q in two patients affected with albright hereditary osteodystrophy. Am. J. Med. Genet. 113, 167-172(2002).
162. Mantovani G, Spada A: Mutations in the Gs a gene causing hormone resistance. Best Pract. Res. Clin. Endocrinol. Metab. 20, 501-513 (2006).
163. Liu J, Erlichman B, Weinstein LS: The stimulatory G protein a-subunit Gs a is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and IB. J. Clin. Endocrinol. Metab. 88, 4336-4341 (2003).
164. Bastepe M, Frohlich LF, Hendy GN et al.: Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. J. Clin. Invest. 112, 1255-1263(2003).
165. Liu J, Litman D, Rosenberg MJ, Yu S, Biesecker LG, Weinstein LS: A GNAS1 imprinting defect in pseudohypoparathyroidism type IB. J. Clin. Invest. 106, 1167-1174 (2000).
166. Bastepe M, Pincus JE, Sugimoto T et al.: Positional dissociation between the genetic mutation responsible for pseudohypoparathyroidism type Ib and the associated methylation defect at exon A/B: evidence for a long-range regulatory element within the imprinted GNAS1 locus. Hum. Mol. Genet. 10, 1231-1241 (2001).
167. Jan de Beur S, Ding C, Germain-Lee E, Cho J, Maret A, Levine MA: Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type lb revealed by inconsistent loss of maternal imprinting at GNASl Am. J. Hum. Genet. 73, 314-322 (2003).
168. Bastepe M, Lane AH, Juppner H: Paternal uniparental isodisomy of chromosome 20q-and the resulting changes in GNASl methylation - as a plausible cause of pseudohypoparathyroidism. Am. J. Hum. Genet. 68, 1283-1289 (2001).
169. El-Maarri O, Seoud M, Coullin P et al.: Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles. Hum. Mol. Genet. 12, 1405-1413 (2003).
170. Fisher RA, Hodges MD, Rees HC et al.: The maternally transcribed gene p57(KIP2) (CDNK1C) is abnormally expressed in both androgenetic and biparental complete hydatidiform moles. Hum. Mol. Genet. 11, 3267-3272 (2002).
171. Judson H, Hayward BE, Sheridan E, Bonthron DT: A global disorder of imprinting in the human female germ line. Nature 416, 539-542 (2002).
172. Murdoch S, Djuric U, Mazhar B et al.: Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat. Genet. 38, 300-302 (2006).
173. Zhang P, Dixon M, Zucchelli M et al.: Expression analysis of the NLRP gene family suggests a role in human preimplantation development. PLoS ONE 3, e2755 (2008).
174. Djuric U, El-Maarri O, Lamb B et al.: Familial molar tissues due to mutations in the inflammatory gene, NALP7, have normal postzygotic DNA methylation. Hum. Genet. 120, 390-395 (2006).
175. Kinoshita T, Wang Y, Hasegawa M, Imamura R, Suda T: PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1β secretion. J. Biol. Chem. 280, 21720-21725 (2005).
176. Drenth JP, van der Meer JW: The inflammasome - a linebacker of innate defense. N. Engl. J. Med. 355, 730-732 (2006).
177. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD: Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat. Genet. 29, 301-305 (2001).
178. Jeru I, Duquesnoy P, Fernandes-Alnemri T et al.: Mutations in NALP12 cause hereditary periodic fever syndromes. Proc. Natl Acad. Sci. USA 105, 1614-1619 (2008).
179. Jin Y, Mailloux CM, Gowan K et al.: NALP1 in vitiligo-associated multiple autoimmune disease. N Engl. J. Med. 356, 1216-1225 (2007).
180. Bestor TH: Cytosine methylation mediates sexual conflict. Trends Genet. 19, 185-190 (2003).
181. Van den Veyver IB, Al-Hussaini TK: Biparental hydatidiform moles: a maternal effect mutation affecting imprinting in the offspring. Hum. Reprod. Update 12, 233-242 (2006).
182. Deveault C, Qian JH, Chebaro W et al.: NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Hum. Mol. Genet. 18, 888-897 (2009).
183. American Association for Cancer Research Human Epigenome Task Force; European Union, Network of Excellence, Scientific Advisory Board: Moving AHEAD with an international human epigenome project. Nature 454, 711-715(2008).
184. Hansen M, Kurinczuk JJ, Bower C, Webb S: The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N. Engl. J. Med. 346, 725-730 (2002).
185. Feinberg AP: Epigenetics at the epicenter of modern medicine. JAMA 299,
186. Van Buggenhout G, Fryns JP: Angelman syndrome (AS, MIM 105830). Eur. J. Hum. Genet. 17(11), 1367-1373 (2009).
187. Wilson LC, Trembath RC: Albright's hereditary osteodystrophy. J. Med. Genet. 31, 779-84 (1994).
188. MRC Harwell website www.mgu.har.mrc.ac.uk/imprinting.impsrables.html