Obésité

, Volume 5, Issue 4, pp 103–108 | Cite as

Comment repérer une obésité génétique ?

Article Original / Original Article
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Résumé

Le développement d’une obésité est parfois lié à des anomalies génétiques rares. On distingue les obésités syndromiques et les formes monogéniques. Les obésités syndromiques sont associées à d’autres anomalies du développement (retard mental, dysmorphie, malformations, atteintes neurosensorielles), la plus fréquente étant le syndrome de Prader-Willi (SPW) dont une des caractéristiques majeures est la présence de troubles du comportement alimentaire incontrôlables. La prise en charge de ces obésités est rendue difficile par la coexistence d’atteintes souvent pluriviscérales et d’anomalies comportementales. La mise en évidence de formes monogéniques d’obésité a permis de progresser dans la compréhension des mécanismes de régulation centrale du poids. En effet, les anomalies génétiques en cause affectent le plus souvent des facteurs clés de la régulation du poids, intervenant dans la voie de la leptine et des mélanocortines, cible essentielle de la leptine dans l’hypothalamus. Ces obésités se caractérisent par un début précoce généralement dans l’enfance avec une prise de poids rapide et sévère. L’approche clinique est importante, car elle permet d’orienter vers une origine génétique pour ainsi permettre un éventuel diagnostic moléculaire et une prise en charge spécialisée et multidisciplinaire.

Mots clés

Obésités syndromiques Monogénique Syndrome de Prader-Willi MC4-R Leptine 

How can we identify obesity with genetic origin?

Abstract

The development of obesity is sometimes related to rare genetic abnormalities. This is the case in syndromic obesities and in monogenic rare mutations. Syndromic obesities are associated with developmental abnormalities (mental retardation, dysmorphic features, malformations, sensorineural deficiency, etc.). The most common of these obesity syndromes is the Prader-Willi syndrome, one of whose major characteristics is the presence of uncontrollable eating disorders. The clinical care of these patients is complex, complicated by the co-existence with plurivisceral abnormalities and behavioral disorders and necessitates the involvement of multiple clinical expertises. Identification of monogenic forms of obesity has led to progress in understanding mechanisms of central body weight regulation. Indeed, the genetic mutations mostly affect key factors related to the leptin and the melanocortin hypothalamic pathways, involved in energy homeostasis regulation. All mutations in these candidate genes lead to hyperphagia and severe obesity occurring soon after birth. A careful clinical observation is important to highlight evidence for a genetic origin. This approach is essential for molecular diagnoses and future research and allows development of specialized and multidisciplinary care.

Keywords

Syndromic obesity Monogenic disease Prader-Willi syndrome MC4-R Leptin 

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Références

  1. 1.
    Chung WK, Leibel RL (2005) Molecular physiology of syndromic obesities in humans. Trends Endocrinol Metab 16:267–72CrossRefPubMedGoogle Scholar
  2. 2.
    Goldstone AP, Beales PL (2008) Genetic obesity syndromes. Front Horm Res 36:37–60CrossRefPubMedGoogle Scholar
  3. 3.
    Santini F, Maffei M, Pelosini C, et al (2009) Melanocortin-4 receptor mutations in obesity. Adv Clin Chem 48:95–109CrossRefPubMedGoogle Scholar
  4. 4.
    Mutch DM, Clement K (2006) Genetics of human obesity. Best Pract Res Clin Endocrinol Metab 20:647–64CrossRefPubMedGoogle Scholar
  5. 5.
    Cassidy SB, Driscoll DJ (2009) Prader-Willi syndrome. Eur J Hum Genet 17:3–13CrossRefPubMedGoogle Scholar
  6. 6.
    Kousta E, Hadjiathanasiou CG, Tolis G, Papathanasiou A (2009) Pleiotropic genetic syndromes with developmental abnormalities associated with obesity. J Pediatr Endocrinol Metab 22:581–92PubMedGoogle Scholar
  7. 7.
    Cohen MM, Hall BD, Smith DW, et al (1973) A new syndrome with hypotonia, obesity, mental deficiency, and facial, oral, ocular, and limb anomalies. J Pediatr 83:280–4CrossRefPubMedGoogle Scholar
  8. 8.
    Kolehmainen J, Black GC, Saarinen A, et al (2003) Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport. Am J Hum Genet 72:1359–69CrossRefPubMedGoogle Scholar
  9. 9.
    Turner G, Gedeon A, Mulley J, et al (1989) Borjeson-Forssman-Lehmann syndrome: clinical manifestations and gene localization to Xq26-27. Am J Med Genet 34:463–9CrossRefPubMedGoogle Scholar
  10. 10.
    Lower KM, Turner G, Kerr BA, et al (2002) Mutations in PHF6 are associated with Borjeson-Forssman-Lehmann syndrome. Nat Genet 32:661–5CrossRefPubMedGoogle Scholar
  11. 11.
    Baumstark A, Lower KM, Sinkus A, et al (2003) Novel PHF6 mutation p.D333del causes Borjeson-Forssman-Lehmann syndrome. J Med Genet 40:e50CrossRefPubMedGoogle Scholar
  12. 12.
    Leshinsky-Silver E, Zinger A, Bibi CN, et al (2002) MEHMO (mental retardation, epileptic seizures, hypogenitalism, microcephaly, obesity): a new X-linked mitochondrial disorder. Eur J Hum Genet 10:226–30CrossRefPubMedGoogle Scholar
  13. 13.
    Holder JL, Butte NF, Zinn AR (2000) Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet 9:101–8CrossRefPubMedGoogle Scholar
  14. 14.
    Faivre L, Cormier-Daire V, Lapierre JM, et al (2002) Deletion of the SIM1 gene (6q16.2) in a patient with a Prader-Willi-like phenotype. J Med Genet 39:594–6CrossRefPubMedGoogle Scholar
  15. 15.
    Katsanis N, Ansley SJ, Badano JL, et al (2001) Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293:2256–9CrossRefPubMedGoogle Scholar
  16. 16.
    Russell-Eggitt IM, Clayton PT, Coffey R, et al (1998) Alstrom syndrome. Report of 22 ases and literature review. Ophthalmology 105:1274–80CrossRefPubMedGoogle Scholar
  17. 17.
    Collin GB, Marshall JD, Ikeda A, et al (2002) Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome. Nat Genet 31:74–8PubMedGoogle Scholar
  18. 18.
    Jackson RS, Creemers JW, Ohagi S, et al (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303–6CrossRefPubMedGoogle Scholar
  19. 19.
    Gibson WT, Farooqi IS, Moreau M, et al (2004) Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab 89:4821–6CrossRefPubMedGoogle Scholar
  20. 20.
    Strobel A, Issad T, Camoin L, et al (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18:213–5CrossRefPubMedGoogle Scholar
  21. 21.
    Clement K, Vaisse C, Lahlou N, et al (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398–401CrossRefPubMedGoogle Scholar
  22. 22.
    Farooqi IS, Wangensteen T, Collins S, et al (2007) Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med 356:237–47CrossRefPubMedGoogle Scholar
  23. 23.
    Krude H, Biebermann H, Luck W, et al (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155–7CrossRefPubMedGoogle Scholar
  24. 24.
    Dubern B, Lubrano-Berthelier C, Mencarelli M, et al (2008) Mutational analysis of the pro-opiomelanocortin gene in French obese children led to the identification of a novel deleterious heterozygous mutation located in the alpha-melanocyte stimulating hormone domain. Pediatr Res 63:211–6CrossRefPubMedGoogle Scholar
  25. 25.
    Yeo GS, Connie-Hung CC, Rochford J, et al (2004) A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci 7:1187–9CrossRefPubMedGoogle Scholar
  26. 26.
    Xu B, Goulding EH, Zang K, et al (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6:736–42CrossRefPubMedGoogle Scholar

Copyright information

© Springer Paris 2010

Authors and Affiliations

  1. 1.centre de référence du syndrome de Prader-Willi, groupe hospitalier Pitié-SalpêtrièrePôle endocrinologie et nutritionParisFrance
  2. 2.Inserm nutriomique U872 (Eq7), centre de recherche des Cordeliersuniversité Pierre-et-Marie-Curie-Paris-VIParisFrance

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