Age- and gender-dependent obesity in individuals with 16p11.2 deletion

Yongguo Yu; Haitao Zhu; David T. Miller; James F. Gusella; Orah S. Platt; Bai-Lin Wu; Yiping Shen

doi:10.1016/j.jgg.2011.08.003

Volume 38 Issue 9

Sep. 2011

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Article Navigation > Journal of Genetics and Genomics > 2011 > 38(9): 403-409

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Age- and gender-dependent obesity in individuals with 16p11.2 deletion

doi: 10.1016/j.jgg.2011.08.003

Yongguo Yu^{a, d},
Haitao Zhu^{a, e},
David T. Miller^{a, c},
James F. Gusella^{b, c},
Orah S. Platt^{a, c},
Bai-Lin Wu^{a, c, e},
Yiping Shen^{a, b, c, d}

a
Department of Laboratory Medicine, Children’s Hospital Boston, Boston, MA 02115, USA
b
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
c
Harvard Medical School, Boston, MA 02115, USA
d
Shanghai Children’s Medical Center, Shanghai Jiaotong University, Shanghai 200127, China
e
Children’s Hospital and Institutes of Biomedical Science, Fudan University, Shanghai 201102, China

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Corresponding author: E-mail address: Bai-lin.Wu@childrens.harvard.edu (Bai-Lin Wu); E-mail address: yiping.shen@childrens.harvard.edu (Yiping Shen)
Received Date: 2011-07-02
Accepted Date: 2011-08-09
Rev Recd Date: 2011-07-29

Available Online: 2011-08-17

Publish Date: 2011-09-20

Abstract

Abstract

Recurrent genomic imbalances at 16p11.2 are genetic risk factors of variable penetrance for developmental delay and autism. Recently, 16p11.2 (chr16:29.5 Mb–30.1 Mb) deletion has also been detected in individuals with early-onset severe obesity. The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown. We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 (chr16:29.5 Mb–30.1 Mb) deletion originally ascertained for their developmental disorders by reviewing their medical records. We found that nine individuals could be classified as obese and six as overweight. These individuals generally had early feeding and growth difficulties, and started to gain excessive weight around 5–6 years of age. Thirteen out of the 18 deletion carriers aged 5 years and older (72%) were overweight or obese, whereas only two of 10 deletion carriers (20%) younger than five were overweight or obese. Males exhibited more severe obesity than females. Thus, the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset, exhibited an age- and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader–Willi syndrome (PWS). Early detection of this deletion will provide opportunity to prevent obesity.
- Obesity,
- Chromosome deletion,
- 16p11.2,
- Developmental delay,
- Autism spectrum disorders,
- Chromosomal microarray analysis,
- Genetic testing

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References(28)

References

[1]	Bijlsma, E.K., Gijsbers, A.C., Schuurs-Hoeijmakers, J.H. et al. Extending the phenotype of recurrent rearrangements of 16p11.2: deletions in mentally retarded patients without autism and in normal individuals Eur. J. Med. Genet., 52 (2009),pp. 77-87
[2]	Bochukova, E.G., Huang, N., Keogh, J. et al. Large, rare chromosomal deletions associated with severe early-onset obesity Nature, 463 (2010),pp. 666-670
[3]	Bölte, S., Ozkara, N., Poustka, F. Autism spectrum disorders and low body weight: is there really a systematic association? Int. J. Eat. Disord., 31 (2002),pp. 349-351
[4]	Butler, M.G., Meaney, F.J. Standards for selected anthropometric measurements in Prader-Willi syndrome Pediatrics, 88 (1991),pp. 853-860
[5]	Chen, A.Y., Kim, S.E., Houtrow, A.J. et al. Prevalence of obesity among children with chronic conditions Obesity (Silver Spring), 18 (2010),pp. 210-213
[6]	Christian, S.L., Brune, C.W., Sudi, J. et al. Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder Biol. Psychiatry, 63 (2008),pp. 1111-1117
[7]	Curtin, C., Bandini, L.G., Perrin, E.C. et al. Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: a chart review BMC Pediatr., 5 (2005),p. 48
[8]	Fernandez, B.A., Roberts, W., Chung, B. et al. J. Med. Genet., 47 (2010),pp. 195-203
[9]	Ghebranious, N., Giampietro, P.F., Wesbrook, F.P. et al. A novel microdeletion at 16p11.2 harbors candidate genes for aortic valve development, seizure disorder, and mild mental retardation Am. J. Med. Genet. A, 143 (2007),pp. 1462-1471
[10]	Glessner, J.T., Wang, K., Cai, G. et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes Nature, 459 (2009),pp. 569-573
[11]	Hanson, E., Nasir, R.H., Fong, A. et al. Cognitive and behavioral characterization of 16p11.2 deletion syndrome J. Dev. Behav. Pediatr., 31 (2010),pp. 649-657
[12]	Kumar, R.A., KaraMohamed, S., Sudi, J. et al. Recurrent 16p11.2 microdeletions in autism Hum. Mol. Genet., 17 (2008),pp. 628-638
[13]	Ledbetter, D.H. Cytogenetic technology–genotype and phenotype N. Engl. J. Med., 359 (2008),pp. 1728-1730
[14]	Marshall, C.R., Noor, A., Vincent, J.B. et al. Structural variation of chromosomes in autism spectrum disorder Am. J. Hum. Genet., 82 (2008),pp. 477-488
[15]	Mills, J.L., Hediger, M.L., Molloy, C.A. et al. Elevated levels of growth-related hormones in autism and autism spectrum disorder Clin. Endocrinol. (Oxf), 67 (2007),pp. 230-237
[16]	Mouridsen, S.E., Rich, B., Isager, T. Body mass index in male and female children with infantile autism Autism, 6 (2002),pp. 197-205
[17]	Mouridsen, S.E., Rich, B., Isager, T. Body mass index in male and female children with pervasive developmental disorders Pediatr. Int., 50 (2008),pp. 569-571
[18]	Rosenfeld, J.A., Coppinger, J., Bejjani, B.A. et al. Speech delays and behavioral problems are the predominant features in individuals with developmental delays and 16p11.2 microdeletions and microduplications J. Neurodev. Disord., 2 (2010),pp. 26-38
[19]	Sebat, J., Lakshmi, B., Malhotra, D. et al. Science, 316 (2007),pp. 445-449
[20]	Shen, Y., Irons, M., Miller, D.T. et al. Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance Clin. Chem., 53 (2007),pp. 2051-2059
[21]	Shimojima, K., Inoue, T., Fujii, Y. et al. A familial 593-kb microdeletion of 16p11.2 associated with mental retardation and hemivertebrae Eur. J. Med. Genet., 52 (2009),pp. 433-435
[22]	Shinawi, M., Liu, P., Kang, S.H. et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioral problems, dysmorphism, epilepsy, and abnormal head size J. Med. Genet., 47 (2010),pp. 332-341
[23]	Shiow, L.R., Paris, K., Akana, M.C. et al. Severe combined immunodeficiency (SCID) and attention deficit hyperactivity disorder (ADHD) associated with a Coronin-1A mutation and a chromosome 16p11.2 deletion Clin. Immunol., 131 (2009),pp. 24-30
[24]	Walters, R.G., Jacquemont, S., Valsesia, A. et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2 Nature, 463 (2010),pp. 671-675
[25]	Weiss, L.A., Shen, Y., Korn, J.M. et al. Association between microdeletion and microduplication at 16p11.2 and autism N. Engl. J. Med., 358 (2008),pp. 667-675
[26]	Whiteley, P., Dodou, K., Todd, L. et al. Body mass index of children from the United Kingdom diagnosed with pervasive developmental disorders Pediatr. Int., 46 (2004),pp. 531-533
[27]	Willer, C.J., Speliotes, E.K., Loos, R.J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation Nat. Genet., 41 (2009),pp. 25-34
[28]	Xiong, N., Ji, C., Li, Y. et al. The physical status of children with autism in China Res. Dev. Disabil., 30 (2009),pp. 70-76