Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay

Journal of Medical Genetics

Volumn 53, Issue 3, 2015, Pages 200-207

  Daoud, Hussein ^a   Zhang, Dong ^b   McMurray, Fiona ^c   Yu, Andrea ^a   Luco, Stephanie M ^a   Vanstone, Jason ^a   Jarinova, Olga ^a   Carson, Nancy ^a   Wickens, James ^b   Shishodia, Shifali ^b   Choi, Hwanho ^b   McDonough, Michael A ^b   Schofield, Christopher J ^b   Harper, Mary Ellen ^c   Dyment, David A ^a   Armour, Christine M ^a  

^a CHILDREN S HOSPITAL OF EASTERN ONTARIO   (Canada)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOGLUTARIC ACID; FTO PROTEIN; N DEMETHYLASE; N METHYLNUCLEOSIDE DEMETHYLASE; PROTEIN; UNCLASSIFIED DRUG; FTO PROTEIN, HUMAN;

AMNIOCENTESIS; ARTICLE; BILATERAL HEARING LOSS; CONGENITAL MALFORMATION; DEVELOPMENTAL DISORDER; ECHOCARDIOGRAPHY; ENZYME ACTIVITY; FACIES; FAILURE TO THRIVE; GROWTH RETARDATION; HEART LEFT VENTRICLE HYPERTROPHY; LIQUID CHROMATOGRAPHY; LOW VISION; MASS SPECTROMETRY; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NEWBORN DISEASE; NEXT GENERATION SEQUENCING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PATENT DUCTUS ARTERIOSUS; PRIORITY JOURNAL; CASE REPORT; FEMALE; GENETIC PREDISPOSITION; GENETICS; HIGH THROUGHPUT SEQUENCING; HUMAN; INFANT;

DEVELOPMENTAL DISABILITIES; FEMALE; GENETIC PREDISPOSITION TO DISEASE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; INFANT; MUTATION, MISSENSE; PROTEINS;

EID: 84960333202     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmedgenet-2015-103399     Document Type: Article

References (29)

1. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007;318:1469-72.
2. Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 2002;419:174-8.
3. Koivisto P, Robins P, Lindahl T, Sedgwick B. Demethylation of 3-methylthymine in DNA by bacterial and human DNA dioxygenases. J Biol Chem 2004;279:40470-4.
4. Falnes PO, Johansen RF, Seeberg E. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature 2002;419:178-82.
5. Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 2003;421:859-63.
6. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C. N6-methyladenosine in nuclear RNA is a major substrate of the obesityassociated FTO. Nat Chem Biol 2011;7:885-7.
7. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316:889-94.
8. Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le StunffC, Bougneres P, Kovacs P, Marre M, Balkau B, Cauchi S, Chevre JC, Froguel P. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007;39:724-6.
9. Fawcett KA, Barroso I. The genetics of obesity: FTO leads the way. Trends Genet 2010;26:266-74.
10. Frayling TM, Ong K. Piecing together the FTO jigsaw. Genome Biol 2011;12:104.
11. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U. Inactivation of the Fto gene protects from obesity. Nature 2009;458:894-8.
12. McMurray F, Church CD, Larder R, Nicholson G, Wells S, Teboul L, Tung YC, Rimmington D, Bosch F, Jimenez V, Yeo GS, O'Rahilly S, Ashcroft FM, Coll AP, Cox RD. Adult onset global loss of the FTO gene alters body composition and metabolism in the mouse. PLoS Genet 2013;9:e1003166.
13. Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM, Cox RD. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 2010;42:1086-92.
14. Meyre D, Proulx K, Kawagoe-Takaki H, Vatin V, Gutierrez-Aguilar R, Lyon D, Ma M, Choquet H, Horber F, Van Hul W, Van Gaal L, Balkau B, Visvikis-Siest S, Pattou F, Farooqi IS, Saudek V, O'Rahilly S, Froguel P, Sedgwick B, Yeo GS. Prevalence of loss-of-function FTO mutations in lean and obese individuals. Diabetes 2010;59:311-18.
15. Deliard S, Panossian S, Mentch FD, Kim CE, Hou C, Frackelton EC, Bradfield JP, Glessner JT, Zhang H, Wang K, Sleiman PM, Chiavacci RM, Berkowitz RI, Hakonarson H, Zhao J, Grant SF. The missense variation landscape of FTO, MC4R, and TMEM18 in obese children of African Ancestry. Obesity (Silver Spring) 2013;21:159-63.
16. Zheng Z, Hong L, Huang X, Yang P, Li J, Ding Y, Yao RE, Geng J, Shen Y, Shen Y, Fu Q, Yu Y. Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity. PLoS ONE 2013;8:e67039.
17. Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O'Rahilly S, Munnich A, Colleaux L. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 2009;85:106-11.
18. Hopkinson RJ, Hamed RB, Rose NR, Claridge TD, Schofield CJ. Monitoring the activity of 2-oxoglutarate dependent histone demethylases by NMR spectroscopy: direct observation of formaldehyde. Chembiochem 2010;11:506-10.
19. Banks JL, Beard HS, Cao Y, Cho AE, Damm W, Farid R, Felts AK, Halgren TA, Mainz DT, Maple JR, Murphy R, Philipp DM, Repasky MP, Zhang LY, Berne BJ, Friesner RA, Gallicchio E, Levy RM. Integrated Modeling Program, Applied Chemical Theory (IMPACT). J Comput Chem 2005;26:1752-80.
20. Li H, Robertson AD, Jensen JH. Very fast empirical prediction and rationalization of protein pKa values. Proteins 2005;61:704-21.
21. Greenidge PA, Kramer C, Mozziconacci JC, Wolf RM. MM/GBSA binding energy prediction on the PDBbind data set: successes, failures, and directions for further improvement. J Chem Inf Model 2013;53:201-9.
22. Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J. Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 2010;464:1205-9.
23. Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 2008;582:3313-19.
24. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, Vagbo CB, Shi Y, Wang WL, Song SH, Lu Z, Bosmans RP, Dai Q, Hao YJ, Yang X, Zhao WM, Tong WM, Wang XJ, Bogdan F, Furu K, Fu Y, Jia G, Zhao X, Liu J, Krokan HE, Klungland A, Yang YG, He C. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 2013;49:18-29.
25. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, Sorek R, Rechavi G. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485:201-6.
26. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 30 UTRs and near stop codons. Cell 2012;149:1635-46.
27. Gulati P, Cheung MK, Antrobus R, Church CD, Harding HP, Tung YC, Rimmington D, Ma M, Ron D, Lehner PJ, Ashcroft FM, Cox RD, Coll AP, O'Rahilly S, Yeo GS. Role for the obesity-related FTO gene in the cellular sensing of amino acids. Proc Natl Acad Sci USA 2013;110:2557-62.
28. Aik W, Demetriades M, Hamdan MK, Bagg EA, Yeoh KK, Lejeune C, Zhang Z, McDonough MA, Schofield CJ. Structural basis for inhibition of the fat mass and obesity associated protein (FTO). J Med Chem 2013;56:3680-8.
29. Clifton IJ, McDonough MA, Ehrismann D, Kershaw NJ, Granatino N, Schofield CJ. Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. J Inorg Biochem 2006;100:644-69.