Characterization of ANKRD11 mutations in humans and mice related to KBG syndrome

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• 作者：Katherina Walz (1) (2)
  Devon Cohen (1)
  Paul M. Neilsen (3)
  Joseph Foster II. (1)
  Francesco Brancati (4) (5)
  Korcan Demir (6)
  Richard Fisher (7)
  Michelle Moffat (8)
  Nienke E. Verbeek (9)
  Kathrine Bj酶rgo (10)
  Adriana Lo Castro (11)
  Paolo Curatolo (11)
  Giuseppe Novelli (5)
  Clemer Abad (1)
  Cao Lei (1)
  Lily Zhang (1)
  Oscar Diaz-Horta (1)
  Juan I. Young (1)
  David F. Callen (3)
  Mustafa Tekin (1)
  
• 刊名：Human Genetics
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：134
• 期：2
• 页码：181-190
• 全文大小：2,238 KB
• 参考文献：1. Barbaric I, Perry MJ, Dear TN, Rodrigues Da Costa A, Salopek D, Marusic A, Hough T, Wells S, Hunter AJ, Cheeseman M, Brown SD (2008) An ENU-induced mutation in the Ankrd11 gene results in an osteopenia-like phenotype in the mouse mutant Yoda. Physiol Genomics 32:311鈥?21. doi:10.1152/physiolgenomics.00116.2007 mics.00116.2007" target="_blank" title="It opens in new window">CrossRef
  2. Barford D (2011) Structure, function and mechanism of the anaphase promoting complex (APC/C). Q Rev Biophys 44:153鈥?90. doi:10.1017/S0033583510000259 CrossRef
  3. Brancati F, Sarkozy A, Dallapiccola B (2006) KBG syndrome. Orphanet J Rare Dis 1:50. doi:10.1186/1750-1172-1-50 CrossRef
  4. Handrigan GR, Chitayat D, Lionel AC, Pinsk M, Vaags AK, Marshall CR, Dyack S, Escobar LF, Fernandez BA, Stegman JC, Rosenfeld JA, Shaffer LG, Goodenberger M, Hodge JC, Cain JE, Babul-Hirji R, Stavropoulos DJ, Yiu V, Scherer SW, Rosenblum ND (2013) Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation. J Med Genet 50:163鈥?73. doi:10.1136/jmedgenet-2012-101288 medgenet-2012-101288" target="_blank" title="It opens in new window">CrossRef
  5. Herrmann J, Pallister PD, Tiddy W, Opitz JM (1975) The KBG syndrome-a syndrome of short stature, characteristic facies, mental retardation, macrodontia and skeletal anomalies. Birth Defects Orig Artic Ser 11:7鈥?8
  6. Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425鈥?79 m.67.1.425" target="_blank" title="It opens in new window">CrossRef
  7. Isrie M, Hendriks Y, Gielissen N, Sistermans EA, Willemsen MH, Peeters H, Vermeesch JR, Kleefstra T, Van Esch H (2012) Haploinsufficiency of ANKRD11 causes mild cognitive impairment, short stature and minor dysmorphisms. Eur J Hum Genet 20:131鈥?33. doi:10.1038/ejhg.2011.105 CrossRef
  8. Kawabe H, Brose N (2011) The role of ubiquitylation in nerve cell development. 聽Nat Rev Neurosci 12(5):251鈥?68 CrossRef
  9. Khalifa M, Stein J, Grau L, Nelson V, Meck J, Aradhya S, Duby J (2013) Partial deletion of ANKRD11 results in the KBG phenotype distinct from the 16q24.3 microdeletion syndrome. Am J Med Genet A 161A:835鈥?40. doi:10.1002/ajmg.a.35739 mg.a.35739" target="_blank" title="It opens in new window">CrossRef
  10. Kumar R, Neilsen PM, Crawford J, McKirdy R, Lee J, Powell JA, Saif Z, Martin JM, Lombaerts M, Cornelisse CJ, Cleton-Jansen AM, Callen DF (2005) FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex. Cancer Res 65:11304鈥?1313. doi:10.1158/0008-5472.CAN-05-0936 CrossRef
  11. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW (2008) Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82:477鈥?88. doi:10.1016/j.ajhg.2007.12.009 CrossRef
  12. Miyatake S, Murakami A, Okamoto N, Sakamoto M, Miyake N, Saitsu H, Matsumoto N (2013) A de novo deletion at 16q24.3 involving ANKRD11 in a Japanese patient with KBG syndrome. Am J Med Genet A 161A:1073鈥?077. doi:10.1002/ajmg.a.35661 mg.a.35661" target="_blank" title="It opens in new window">CrossRef
  13. Mosavi LK, Cammett TJ, Desrosiers DC, Peng ZY (2004) The ankyrin repeat as molecular architecture for protein recognition. Protein Sci 13:1435鈥?448. doi:10.1110/ps.03554604 CrossRef
  14. Neilsen PM, Cheney KM, Li CW, Chen JD, Cawrse JE, Schulz RB, Powell JA, Kumar R, Callen DF (2008) Identification of ANKRD11 as a p53 coactivator. J Cell Sci 121:3541鈥?552. doi:10.1242/jcs.026351 CrossRef
  15. Sacharow S, Li D, Fan YS, Tekin M (2012) Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG-like syndrome. Am J Med Genet A 158A:547鈥?52. doi:10.1002/ajmg.a.34436 mg.a.34436" target="_blank" title="It opens in new window">CrossRef
  16. Sirmaci A, Spiliopoulos M, Brancati F, Powell E, Duman D, Abrams A, Bademci G, Agolini E, Guo S, Konuk B, Kavaz A, Blanton S, Digilio MC, Dallapiccola B, Young J, Zuchner S, Tekin M (2011) Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia. Am J Hum Genet 89:289鈥?94. doi:10.1016/j.ajhg.2011.06.007 CrossRef
  17. Skjei KL, Martin MM, Slavotinek AM (2007) KBG syndrome: report of twins, neurological characteristics, and delineation of diagnostic criteria. Am J Med Genet A 143:292鈥?00. doi:10.1002/ajmg.a.31597 mg.a.31597" target="_blank" title="It opens in new window">CrossRef
  18. Spengler S, Oehl-Jaschkowitz B, Begemann M, Hennes P, Zerres K, Eggermann T (2013) Haploinsufficiency of ANKRD11 (16q24.3) is not obligatorily associated with cognitive impairment but shows a clinical overlap with Silver鈥揜ussell syndrome. Mol Syndromol 4:246鈥?49. doi:10.1159/000351765 CrossRef
  19. Tai HC, Schuman EM (2008) Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci 11:826鈥?38 CrossRef
  20. Tarassov K, Messier V, Landry CR, Radinovic S, Serna Molina MM, Shames I, Malitskaya Y, Vogel J, Bussey H, Michnick SW (2008) An in vivo map of the yeast protein interactome. Science 320:1465鈥?470. doi:10.1126/science.1153878 CrossRef
  21. Walz K, Caratini-Rivera S, Bi W, Fonseca P, Mansouri DL, Lynch J, Vogel H, Noebels JL, Bradley A, Lupski JR (2003) Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance. Mol Cell Biol 23:3646鈥?655 CrossRef
  22. Willemsen MH, Fernandez BA, Bacino CA, Gerkes E, de Brouwer AP, Pfundt R, Sikkema-Raddatz B, Scherer SW, Marshall CR, Potocki L, van Bokhoven H, Kleefstra T (2010) Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome. Eur J Hum Genet 18:429鈥?35. doi:10.1038/ejhg.2009.192 CrossRef
  23. Wysocka J, Reilly PT, Herr W (2001) Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells. Mol Cell Biol 21:3820鈥?829. doi:10.1128/MCB.21.11.3820-3829.2001 CrossRef
  24. Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, Li H, Chen JD (2004) Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators. J Biol Chem 279:33799鈥?3805. doi:10.1074/jbc.M403997200 CrossRef
  25. Zhang A, Li CW, Chen JD (2007) Characterization of transcriptional regulatory domains of ankyrin repeat cofactor-1. Biochem Biophys Res Commun 358:1034鈥?040. doi:10.1016/j.bbrc.2007.05.017 CrossRef
  
• 作者单位：Katherina Walz (1) (2)
  Devon Cohen (1)
  Paul M. Neilsen (3)
  Joseph Foster II. (1)
  Francesco Brancati (4) (5)
  Korcan Demir (6)
  Richard Fisher (7)
  Michelle Moffat (8)
  Nienke E. Verbeek (9)
  Kathrine Bj酶rgo (10)
  Adriana Lo Castro (11)
  Paolo Curatolo (11)
  Giuseppe Novelli (5)
  Clemer Abad (1)
  Cao Lei (1)
  Lily Zhang (1)
  Oscar Diaz-Horta (1)
  Juan I. Young (1)
  David F. Callen (3)
  Mustafa Tekin (1)
  
  1. Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, 1501 NW 10 Ave, BRB 610, M-860, Miami, FL, 33136, USA
  2. Department of Medicine, Miller School of Medicine, University of Miami, 1501 NW 10 Ave, BRB 418, M-860, Miami, FL, 33136, USA
  3. Swinburne University of Technology Sarawak Campus, Kuching, Sarawak, Malaysia
  4. Department of Medical, Oral and Biotechnological Sciences, Gabriele D鈥橝nnunzio University, 66100, Chieti, Italy
  5. Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Viale Oxford 81, 00133, Rome, Italy
  6. Division of Pediatric Endocrinology, Dokuz Eyl眉l University Faculty of Medicine, 陌zmir, 35340, Turkey
  7. Northern Genetics Service Teesside Genetics Unit, The James Cook University Hospital, Marton Road, Middlesbrough, TS4 3BW, UK
  8. Department of Paediatric Dentistry, Newcastle Dental Hospital and School, Richardson Road, Newcastle upon Tyne, NE2 4AZ, UK
  9. Department of Medical Genetics, University Medical Center Utrecht, Lundlaan 6, 3584 EA, Utrecht, The Netherlands
  10. Department of Medical Genetics, Oslo University Hospital, Kirkeveien 166, 0450, Oslo, Norway
  11. Department of Neuroscience, Pediatric Neurology and Psychiatry Unit, Tor Vergata University of Rome, 00165, Rome, Italy
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Molecular Medicine
  Internal Medicine
  Metabolic Diseases
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1203

文摘

Mutations in ANKRD11 have recently been reported to cause KBG syndrome, an autosomal dominant condition characterized by intellectual disability (ID), behavioral problems, and macrodontia. To understand the pathogenic mechanism that relates ANKRD11 mutations with the phenotype of KBG syndrome, we studied the cellular characteristics of wild-type ANKRD11 and the effects of mutations in humans and mice. We show that the abundance of wild-type ANKRD11 is tightly regulated during the cell cycle, and that the ANKRD11 C-terminus is required for the degradation of the protein. Analysis of 11 pathogenic ANKRD11 variants in humans, including six reported in this study, and one reported in the Ankrd11 Yod/+ mouse, shows that all mutations affect the C-terminal regions and that the mutant proteins accumulate aberrantly. In silico analysis shows the presence of D-box sequences that are signals for proteasome degradation. We suggest that ANKRD11 C-terminus plays an important role in regulating the abundance of the protein, and a disturbance of the protein abundance due to the mutations leads to KBG syndrome.