title: Epigenetics and Human Disease.
abstract: Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation. Disease may be caused by direct changes in epigenetic marks, such as DNA methylation, commonly found to affect imprinted gene regulation. Also described are disease-causing genetic mutations in epigenetic modifiers that either affect chromatin in trans or have a cis effect in altering chromatin configuration.
authors.affiliation: Howard Hughes Medical Institute, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
mesh_terms: D004194:Disease / Q000235:genetics*; D044127:Epigenesis, Genetic; D006801:Humans
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5203-8
references.pmid: 10220444
references.citation: Curr Opin Genet Dev. 1999 Apr;9(2):152-7
references.pmid: 10322132
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8064-9
references.pmid: 10393948
references.citation: Hum Mol Genet. 1999 Aug;8(8):1357-64
references.pmid: 10400982
references.citation: Nat Genet. 1999 Oct;23(2):185-8
references.pmid: 10508514
references.citation: Cell. 1999 Oct 29;99(3):247-57
references.pmid: 10555141
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13983-8
references.pmid: 10570185
references.citation: Am J Hum Genet. 1999 Dec;65(6):1520-9
references.pmid: 10577905
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14412-7
references.pmid: 10588719
references.citation: Genes Dev. 1999 Dec 1;13(23):3115-24
references.pmid: 10601037
references.citation: Nature. 1999 Nov 11;402(6758):187-91
references.pmid: 10647011
references.citation: Hum Mol Genet. 2000 Mar 1;9(4):597-604
references.pmid: 10699183
references.citation: Nature. 2000 May 25;405(6785):486-9
references.pmid: 10839547
references.citation: Cytogenet Cell Genet. 2000;89(1-2):121-8
references.pmid: 10894953
references.citation: Am J Hum Genet. 2000 Oct;67(4):982-5
references.pmid: 10986043
references.citation: Am J Clin Nutr. 2000 Oct;72(4):998-1003
references.pmid: 11010943
references.citation: Hum Mol Genet. 2001 Apr 15;10(9):941-6
references.pmid: 11309367
references.citation: Hum Mol Genet. 2001 May 1;10(10):1071-6
references.pmid: 11331617
references.citation: J Biol Chem. 2001 Aug 24;276(34):32282-7
references.pmid: 11427539
references.citation: Hum Mol Genet. 2001 Dec 1;10(25):2917-31
references.pmid: 11741835
references.citation: Hum Mol Genet. 2001 Dec 15;10(26):2989-3000
references.pmid: 11751681
references.citation: Nat Genet. 2002 Feb;30(2):215-20
references.pmid: 11799392
references.citation: Hum Mol Genet. 2002 Jan 15;11(2):115-24
references.pmid: 11809720
references.citation: J Child Neurol. 2002 Jan;17(1):20-4
references.pmid: 11913564
references.citation: J Biol Chem. 2002 Jun 7;277(23):20409-14
references.pmid: 11919202
references.citation: Am J Med Genet. 2002 Jul 1;110(3):243-7
references.pmid: 12116232
references.citation: Cell. 2002 Aug 9;110(3):339-48
references.pmid: 12176321
references.citation: Am J Hum Genet. 2002 Oct;71(4):923-32
references.pmid: 12232854
references.citation: Nat Genet. 2002 Oct;32(2):235-6
references.pmid: 12355084
references.citation: Am J Hum Genet. 2003 Jan;72(1):156-60
references.pmid: 12439823
references.citation: Hum Mol Genet. 2002 Dec 15;11(26):3267-72
references.pmid: 12471053
references.citation: J Med Genet. 2002 Dec;39(12):872-5
references.pmid: 12471198
references.citation: Am J Hum Genet. 2003 Jan;72(1):218-9
references.pmid: 12549484
references.citation: Nature. 2003 Feb 13;421(6924):686-8
references.pmid: 12610592
references.citation: Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R61-8
references.pmid: 12668598
references.citation: Hum Mol Genet. 2003 May 1;12(9):949-59
references.pmid: 12700164
references.citation: Lancet. 2003 May 17;361(9370):1693-9
references.pmid: 12767735
references.citation: Pediatr Neurol. 2003 Mar;28(3):205-11
references.pmid: 12770674
references.citation: Nat Genet. 2003 Aug;34(4):446-9
references.pmid: 12858175
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R207-13
references.pmid: 12915455
references.citation: Neuron. 2003 Aug 28;39(5):739-47
references.pmid: 12948442
references.citation: Nat Genet. 1992 Sep;2(1):26-30
references.pmid: 1363881
references.citation: J Clin Invest. 2003 Oct;112(8):1255-63
references.pmid: 14561710
references.citation: Am J Med Genet. 1992 Sep 15;44(2):237-41
references.pmid: 1456298
references.citation: Nucleic Acids Res. 2003 Nov 1;31(21):6243-8
references.pmid: 14576312
references.citation: Clin Immunol. 2003 Oct;109(1):17-28
references.pmid: 14585272
references.citation: Neurol Clin. 2003 Nov;21(4):795-816
references.pmid: 14743650
references.citation: Neuroscience. 2004;123(4):939-49
references.pmid: 14751287
references.citation: Cell Mol Life Sci. 2004 Mar;61(5):557-566
references.pmid: 15004695
references.citation: Am J Hum Genet. 2004 May;74(5):805-16
references.pmid: 15052536
references.citation: Nat Genet. 2004 May;36(5):497-501
references.pmid: 15064764
references.citation: Biol Psychiatry. 2004 May 15;55(10):965-70
references.pmid: 15121478
references.citation: Neuron. 2004 Jun 24;42(6):947-59
references.pmid: 15207239
references.citation: Nat Neurosci. 2004 Aug;7(8):847-54
references.pmid: 15220929
references.citation: Hum Mol Genet. 2004 Nov 1;13(21):2679-89
references.pmid: 15351775
references.citation: N Engl J Med. 1992 Mar 19;326(12):807-11
references.pmid: 1538725
references.citation: Nat Cell Biol. 2004 Nov;6(11):1048-53
references.pmid: 15516998
references.citation: Mol Cell Neurosci. 2004 Nov;27(3):306-21
references.pmid: 15519245
references.citation: Am J Med Genet A. 2004 Dec 1;131(2):194-9
references.pmid: 15523612
references.citation: J Clin Invest. 2005 Feb;115(2):258-67
references.pmid: 15668733
references.citation: J Med Genet. 2005 Feb;42(2):e12
references.pmid: 15689435
references.citation: Am J Hum Genet. 2005 Apr;76(4):572-80
references.pmid: 15706485
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4085-90
references.pmid: 15743916
references.citation: J Med Genet. 2005 Apr;42(4):289-91
references.pmid: 15805153
references.citation: BMC Med Genet. 2005 May 06;6:18
references.pmid: 15877813
references.citation: Science. 2005 Jun 3;308(5727):1466-9
references.pmid: 15933200
references.citation: Eur J Hum Genet. 2005 Sep;13(9):1025-32
references.pmid: 15999116
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references.pmid: 16009939
references.citation: Cell. 1992 Jun 12;69(6):905-14
references.pmid: 1606614
references.citation: Am J Hum Genet. 2005 Sep;77(3):442-53
references.pmid: 16080119
references.citation: Nat Genet. 2005 Sep;37(9):1003-7
references.pmid: 16086014
references.citation: Biol Psychiatry. 2006 Mar 1;59(5):468-76
references.pmid: 16199017
references.citation: Nat Genet. 2006 Mar;38(3):300-2
references.pmid: 16462743
references.citation: Nature. 1991 Jun 20;351(6328):665-7
references.pmid: 1675767
references.citation: Cell. 1991 May 31;65(5):905-14
references.pmid: 1710175
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1931-6
references.pmid: 17267601
references.citation: Science. 2007 Feb 23;315(5815):1143-7
references.pmid: 17289941
references.citation: Hum Mol Genet. 2008 Mar 1;17(5):690-709
references.pmid: 18029387
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19416-21
references.pmid: 18042715
references.citation: Nat Genet. 2008 Feb;40(2):237-42
references.pmid: 18176563
references.citation: Cell Stem Cell. 2007 Nov;1(5):568-77
references.pmid: 18371394
references.citation: Nat Genet. 2008 Jun;40(6):719-21
references.pmid: 18500341
references.citation: Science. 2008 May 30;320(5880):1224-9
references.pmid: 18511691
references.citation: Cell. 1991 Aug 23;66(4):817-22
references.pmid: 1878973
references.citation: Neuron. 2008 Sep 25;59(6):947-58
references.pmid: 18817733
references.citation: Nat Neurosci. 2009 Mar;12(3):311-7
references.pmid: 19234456
references.citation: Exp Neurol. 2009 Sep;219(1):104-11
references.pmid: 19427855
references.citation: BMC Biol. 2009 Jul 16;7:41
references.pmid: 19607661
references.citation: J Physiol Pharmacol. 2009 Oct;60 Suppl 3:17-35
references.pmid: 19996479
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21966-71
references.pmid: 20007372
references.citation: Ann Neurol. 2009 Dec;66(6):771-82
references.pmid: 20035514
references.citation: Mol Cell. 2010 Feb 26;37(4):457-68
references.pmid: 20188665
references.citation: J Pediatr. 1991 Jul;119(1 Pt 1):64-72
references.pmid: 2066860
references.citation: Nat Genet. 2010 Sep;42(9):790-3
references.pmid: 20711175
references.citation: Nature. 2010 Nov 11;468(7321):263-9
references.pmid: 21068835
references.citation: J Cell Biol. 2010 Dec 13;191(6):1049-60
references.pmid: 21149563
references.citation: Nucleus. 2010 May-Jun;1(3):245-8
references.pmid: 21327070
references.citation: Am J Clin Nutr. 2011 Dec;94(6 Suppl):1953S-1958S
references.pmid: 21543542
references.citation: Am J Hum Genet. 2011 Jun 10;88(6):796-804
references.pmid: 21596365
references.citation: J Neurol Psychiatry. 1943 Jul;6(3-4):154-7
references.pmid: 21611430
references.citation: Science. 2011 Jul 8;333(6039):186
references.pmid: 21636743
references.citation: Am J Med Genet A. 2011 Jul;155A(7):1511-6
references.pmid: 21671394
references.citation: Curr Probl Pediatr Adolesc Health Care. 2011 Jul;41(6):158-76
references.pmid: 21684471
references.citation: Nature. 2011 Jun 29;475(7357):497-500
references.pmid: 21716289
references.citation: J Neurosci. 2011 Jul 13;31(28):10359-70
references.pmid: 21753013
references.citation: Semin Reprod Med. 2011 May;29(3):266-76
references.pmid: 21769766
references.citation: Am J Hum Genet. 2011 Sep 9;89(3):451-8
references.pmid: 21885028
references.citation: Hum Mutat. 2012 Jan;33(1):180-8
references.pmid: 21953887
references.citation: PLoS One. 2011;6(10):e26203
references.pmid: 22022567
references.citation: Am J Hum Genet. 2012 Jan 13;90(1):119-24
references.pmid: 22197486
references.citation: Nature. 2012 Mar 18;484(7392):105-9
references.pmid: 22425995
references.citation: Hum Mol Genet. 2012 Jul 1;21(13):3001-12
references.pmid: 22493002
references.citation: Genes Dev. 1990 Oct;4(10):1637-49
references.pmid: 2249769
references.citation: Brain. 2012 Sep;135(Pt 9):2699-710
references.pmid: 22525157
references.citation: Cell. 2012 May 11;149(4):819-31
references.pmid: 22541069
references.citation: Expert Rev Mol Diagn. 2012 Jun;12(5):459-71
references.pmid: 22702363
references.citation: Eur J Hum Genet. 2012 Dec;20(12):1256-64
references.pmid: 22763379
references.citation: ISRN Obstet Gynecol. 2012;2012:405382
references.pmid: 22778982
references.citation: Hum Mol Genet. 2012 Nov 1;21(21):4669-79
references.pmid: 22843497
references.citation: Genet Med. 2013 Jan;15(1):25-35
references.pmid: 22878509
references.citation: Front Genet. 2012 Oct 08;3:199
references.pmid: 23060903
references.citation: Cell. 2012 Dec 21;151(7):1417-30
references.pmid: 23260135
references.citation: Cell Rep. 2013 Feb 21;3(2):291-300
references.pmid: 23403289
references.citation: Nature. 2013 Aug 8;500(7461):222-6
references.pmid: 23812591
references.citation: Trends Biochem Sci. 2013 Sep;38(9):461-6
references.pmid: 23916100
references.citation: J Neurosci. 2013 Aug 21;33(34):13612-20
references.pmid: 23966684
references.citation: Nat Genet. 2013 Nov;45(11):1405-8
references.pmid: 24076603
references.citation: PLoS Genet. 2013;9(12):e1004039
references.pmid: 24385930
references.citation: Cold Spring Harb Perspect Biol. 2014 Feb 01;6(2):null
references.pmid: 24492710
references.citation: Neuron. 2014 Apr 2;82(1):94-108
references.pmid: 24698270
references.citation: Int Rev Cytol. 1989;114:181-220
references.pmid: 2472365
references.citation: Cold Spring Harb Perspect Biol. 2014 May 01;6(5):a019133
references.pmid: 24789823
references.citation: Cold Spring Harb Perspect Biol. 2014 Aug 01;6(8):null
references.pmid: 25085913
references.citation: Cold Spring Harb Perspect Biol. 2014 Oct 01;6(10):a018630
references.pmid: 25274704
references.citation: Cold Spring Harb Perspect Biol. 2015 Jan 05;7(1):a018622
references.pmid: 25561718
references.citation: Am J Hum Genet. 1989 May;44(5):720-3
references.pmid: 2565083
references.citation: Cold Spring Harb Perspect Biol. 2015 Mar 02;7(3):a019406
references.pmid: 25731764
references.citation: Mutat Res. 1989 Sep-Nov;219(5-6):263-6
references.pmid: 2615776
references.citation: Cold Spring Harb Perspect Biol. 2015 Sep 01;7(9):a025064
references.pmid: 26330523
references.citation: Cold Spring Harb Perspect Biol. 2015 Oct 01;7(10):a019356
references.pmid: 26430217
references.citation: Cold Spring Harb Perspect Biol. 2016 Nov 1;8(11):null
references.pmid: 26492570
references.citation: Cold Spring Harb Perspect Biol. 2016 Jan 04;8(1):a019547
references.pmid: 26729649
references.citation: Trends Genet. 1989 Oct;5(10):331-6
references.pmid: 2692240
references.citation: Cold Spring Harb Perspect Biol. 2016 Apr 01;8(4):a019521
references.pmid: 27037415
references.citation: Cold Spring Harb Perspect Biol. 2016 May 02;8(5):
references.pmid: 27141050
references.citation: Cold Spring Harb Perspect Biol. 2016 Sep 01;8(9):null
references.pmid: 27194046
references.citation: Cold Spring Harb Perspect Biol. 2016 Jul 01;8(7):
references.pmid: 27371659
references.citation: Proc Natl Acad Sci U S A. 1989 Oct;86(19):7470-4
references.pmid: 2798417
references.citation: Nature. 1989 Nov 16;342(6247):281-5
references.pmid: 2812027
references.citation: Am J Hum Genet. 1988 Feb;42(2):217-26
references.pmid: 2893543
references.citation: J Clin Invest. 1985 Oct;76(4):1554-8
references.pmid: 2997283
references.citation: Am J Med Genet. 1987 Dec;28(4):829-38
references.pmid: 3688021
references.citation: Lancet. 1971 Nov 13;2(7733):1088-9
references.pmid: 4106927
references.citation: Nature. 1977 Aug 18;268(5621):633-4
references.pmid: 561314
references.citation: Am J Hum Genet. 1969 May;21(3):231-44
references.pmid: 5794013
references.citation: Lancet. 1984 Jul 28;2(8396):196-8
references.pmid: 6146753
references.citation: Nature. 1983 Dec 15-21;306(5944):662-6
references.pmid: 6318113
references.citation: Ann Neurol. 1983 Oct;14(4):471-9
references.pmid: 6638958
references.citation: J Med Genet. 1983 Aug;20(4):280-5
references.pmid: 6684694
references.citation: Hum Genet. 1984;65(4):325-30
references.pmid: 6693121
references.citation: Am J Med Genet. 1984 Jan;17(1):111-21
references.pmid: 6711590
references.citation: Am J Med Genet. 1980;6(2):137-43
references.pmid: 7192492
references.citation: J Ment Defic Res. 1981 Dec;25 Pt 4:253-6
references.pmid: 7328634
references.citation: N Engl J Med. 1981 Feb 5;304(6):325-9
references.pmid: 7442771
references.citation: Drugs. 1994 Aug;48(2):137-52
references.pmid: 7527320
references.citation: Nature. 1995 Jul 27;376(6538):348-51
references.pmid: 7630403
references.citation: Cell. 1995 Mar 24;80(6):837-45
references.pmid: 7697714
references.citation: Nat Genet. 1994 Aug;7(4):536-40
references.pmid: 7951326
references.citation: Hum Genet. 1994 Sep;94(3):240-6
references.pmid: 8076938
references.citation: Hum Mol Genet. 1993 Jun;2(6):731-5
references.pmid: 8102570
references.citation: Hum Mol Genet. 1993 Dec;2(12):2037-42
references.pmid: 8111371
references.citation: Growth Dev Aging. 1993 Winter;57(4):261-73
references.pmid: 8300279
references.citation: Hum Mol Genet. 1993 May;2(5):549-56
references.pmid: 8518793
references.citation: Nat Genet. 1996 Apr;12(4):359-60
references.pmid: 8630485
references.citation: Ann Neurol. 1996 Aug;40(2):254-7
references.pmid: 8773611
references.citation: Science. 1977 Jul 15;197(4300):265-6
references.pmid: 877551
references.citation: Cell. 1996 Nov 29;87(5):953-9
references.pmid: 8945521
references.citation: Hum Mol Genet. 1996 Dec;5(12):1899-907
references.pmid: 8968741
references.citation: Nat Genet. 1997 Jan;15(1):70-3
references.pmid: 8988171
references.citation: Nat Genet. 1997 Jan;15(1):74-7
references.pmid: 8988172
references.citation: Cell. 1997 Feb 21;88(4):471-81
references.pmid: 9038338
references.citation: Hum Genet. 1997 Sep;100(3-4):415-9
references.pmid: 9272165
references.citation: Hum Mol Genet. 1997 Sep;6(9):1543-8
references.pmid: 9285792
references.citation: Science. 1997 Sep 12;277(5332):1659-62
references.pmid: 9287218
references.citation: Nature. 1997 Oct 23;389(6653):809-15
references.pmid: 9349812
references.citation: Nat Genet. 1998 May;19(1):15-6
references.pmid: 9590281
references.citation: Nat Genet. 1998 Jun;19(2):187-91
references.pmid: 9620779
references.citation: Nature. 1998 May 28;393(6683):386-9
references.pmid: 9620804
references.citation: FASEB J. 1998 Aug;12(11):949-57
references.pmid: 9707167
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10038-43
references.pmid: 9707596
references.citation: Neuron. 1998 Oct;21(4):799-811
references.pmid: 9808466
references.citation: Am J Hum Genet. 1999 Feb;64(2):397-413
references.pmid: 9973278