X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face

Journal of Medical Genetics

Volumn 49, Issue 8, 2012, Pages 539-543

  Harakalova, Magdalena ^a   van den Boogaard, Marie Jose ^a   Sinke, Richard ^b   van Lieshout, Stef ^a   van Tuil, Marc C ^a   Duran, Karen ^a   Renkens, Ivo ^a   Terhal, Paulien A ^a   de Kovel, Carolien ^a   Nijman, Ies J ^a   van Haelst, Mieke ^a   Knoers, Nine V A M ^a   van Haaften, Gijs ^a   Kloosterman, Wigard ^a   Hennekam, Raoul C M ^c   Cuppen, Edwin ^a   van Amstel, Hans Kristian Ploos ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE DEACETYLASE 8;

ARTICLE; CHROMOSOME MUTATION; CRANIOFACIAL MALFORMATION; ENZYME ACTIVE SITE; EPIGENETICS; EXOME; EXON; FEMALE; GENE; GENE SILENCING; GENETIC VARIABILITY; GYNECOMASTIA; HDAC8 GENE; HUMAN; HUMAN CELL; HYPOGONADISM; INTRON; MALE; MALFORMATION SYNDROME; NETHERLANDS; OBESITY; PEDIGREE; PHENOTYPE; PRIORITY JOURNAL; WILSON TURNER SYNDROME; X CHROMOSOMAL INHERITANCE; X CHROMOSOME INACTIVATION; X CHROMOSOME LINKED DISORDER; X LINKED INTELLECTUAL DISABILITY;

CASE-CONTROL STUDIES; CHROMOSOMES, HUMAN, X; CRANIOFACIAL ABNORMALITIES; DNA MUTATIONAL ANALYSIS; EXOME; EXONS; FEMALE; GENETIC LOCI; GENETIC TESTING; GYNECOMASTIA; HETEROZYGOTE; HISTONE DEACETYLASES; HUMANS; HYPOGONADISM; INTRONS; MALE; MENTAL RETARDATION, X-LINKED; MUTATION; NETHERLANDS; OBESITY, ABDOMINAL; PEDIGREE; PHENOTYPE; REPRESSOR PROTEINS; SYNDROME; X CHROMOSOME INACTIVATION;

EID: 84866329518     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2012-100921     Document Type: Article

References (20)

1. Gecz J, Shoubridge C, Corbett M. The genetic landscape of intellectual disability arising from chromosome X. Trends Genet 2009;25:308-16.
2. Stevenson RE, Schwartz CE. X-linked intellectual disability: unique vulnerability of the male genome. Dev Disabil Res Rev 2009;15:361-8.
3. Ropers HH. Genetics of early onset cognitive impairment. Annu Rev Genomics Hum Genet 2010;11:161-87.
4. Gecz J, Turner G, Nelson J, Partington M. The Borjeson-Forssman-Lehman syndrome (BFLS, MIM #301900). Eur J Hum Genet 2006;14:1233-7.
5. Wilson M, Mulley J, Gedeon A, Robinson H, Turner G. New X-linked syndrome of mental retardation, gynecomastia, and obesity is linked to DXS255. Am J Med Genet 1991;40:406-13.
6. Harakalova M, Mokry M, Hrdlickova B, Renkens I, Duran K, van Roekel H, Lansu N, van Roosmalen M, de Bruijn E, Nijman IJ, Kloosterman WP, Cuppen E. Multiplexed array-based and in-solution genomic enrichment for flexible and cost-effective targeted next-generation sequencing. Nat Protoc 2011;6:1870-86.
7. Balasubramanian S, Verner E, Buggy JJ. Isoform-specific histone deacetylase inhibitors: the next step? Cancer Lett 2009;280:211-21.
8. Wutz A. Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation. Nat Rev Genet 2011;12:542-53.
9. Plenge RM, Stevenson RA, Lubs HA, Schwartz CE, Willard HF. Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders. Am J Hum Genet 2002;71:168-73.
10. Cottrell CE, Sommer A, Wenger GD, Bullard S, Busch T, Krahn KN, Lidral AC, Gastier-Foster JM. Atypical X-chromosome inactivation in an X;1 translocation patient demonstrating Xq28 functional disomy. Am J Med Genet A 2009;149A:408-14.
11. Brinkman AB, Roelofsen T, Pennings SW, Martens JH, Jenuwein T, Stunnenberg HG. Histone modification patterns associated with the human X chromosome. EMBO Rep 2006;7:628-34.
12. Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V. An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha. Mol Endocrinol 2010;24:1349-58.
13. Hayakawa T, Nakayama J. Physiological roles of class I HDAC complex and histone demethylase. J Biomed Biotechnol 2011;2011:129383.
14. Franklin TB, Mansuy IM. The involvement of epigenetic defects in mental retardation. Neurobiol Learn Mem 2011;96:61-7.
15. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 2008;7:854-68.
16. Williams SR, Aldred MA, Der Kaloustian VM, Halal F, Gowans G, McLeod DR, Zondag S, Toriello HV, Magenis RE, Elsea SH. Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems. Am J Hum Genet 2010;87:219-28.
17. Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, Richieri-Costa A, Zackai EH, Massagué J, Muenke M, Elledge SJ. Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Nat Genet 2000;25:205-8.
18. Bochar DA, Savard J, Wang W, Lafleur DW, Moore P, Côté J, Shiekhattar R. A family of chromatin remodeling factors related to Williams syndrome transcription factor. Proc Natl Acad Sci USA 2000;97:1038-43.
19. Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R. A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci USA 2002;99:7420-5.
20. Haberland M, Mokalled MH, Montgomery RL, Olson EN. Epigenetic control of skull morphogenesis by histone deacetylase 8. Genes Dev 2009;23:1625-30.