Mutational analysis of the pro-opiomelanocortin gene in French obese children led to the identification of a novel deleterious heterozygous mutation located in the α-melanocyte stimulating hormone domain

Pediatric Research

Volumn 63, Issue 2, 2008, Pages 211-216

  Dubern, Beatrice ^a,b,c,e   Lubrano Berthelier, Cecile ^a,b,c,d   Mencarelli, Monica ^a,b,c,l   Ersoy, Baran ^f   Frelut, Marie Laure ^g   BouglI, Dominique ^h   Costes, Bruno ^i,j   Simon, Chantal ^k   Tounian, Patrick ^a,b,c,e   Vaisse, Christian ^f   Clement, Karine ^a,b,c,d  

^a Human Nutrition Research Center Ile de France   (France)

^b CENTRE DE RECHERCHE DES CORDELIERS   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d HÔTEL DIEU   (France)

^e ARMAND TROUSSEAU HOSPITAL   (France)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g French Red Cross   (France)

^h CAEN UNIVERSITY HOSPITAL   (France)

ⁱ HENRI MONDOR HOSPITAL   (France)

^j INSERM   (France)

^k UNIVERSITÉ DE STRASBOURG   (France)

^l ISTITUTO AUXOLOGICO ITALIANO   (Italy)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERMEDIN; PROOPIOMELANOCORTIN;

ADOLESCENT; ARTICLE; CHILD; CONTROLLED STUDY; DEMOGRAPHY; DISEASE ASSOCIATION; FEMALE; GENE MUTATION; GENE SEQUENCE; GENETIC VARIABILITY; HUMAN; MAJOR CLINICAL STUDY; MALE; MUTATIONAL ANALYSIS; OBESITY; PHENOTYPE; PRIORITY JOURNAL;

ALPHA-MSH; CHILD; DNA MUTATIONAL ANALYSIS; FRANCE; GENE EXPRESSION REGULATION; HETEROZYGOTE; HUMANS; LEUCINE; MODELS, BIOLOGICAL; MODELS, GENETIC; MUTATION; OBESITY; PHENYLALANINE; PRO-OPIOMELANOCORTIN; PROTEIN BINDING;

EID: 38349151344     PISSN: 00313998     EISSN: None     Source Type: Journal    
DOI: 10.1203/PDR.0b013e31815ed62b     Document Type: Article

References (28)

1. Cone RD 2006 Studies on the physiological functions of the melanocortin system. Endocr Rev 27:736-749
2. Seeley RJ, Drazen DL, Clegg DJ 2004 The critical role of the melanocortin system in the control of energy balance. Annu Rev Nutr 24:133-149
3. Slominski A, Plonka PM, Pisarchik A, Smart JL, Tolle V, Wortsman J, Low MJ 2005 Preservation of eumelanin hair pigmentation in proopiomelanocortin- deficient mice on a nonagouti (a/a) genetic background. Endocrinology 146:1245-1253
4. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A 1998 Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155-157
5. Farooqi IS, Drop S, Clements A, Keogh JM, Biernacka J, Lowenbein S, Challis BG, O'Rahilly S 2006 Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes 55:2549-2553
6. Comuzzie AG, Hixson JE, Almasy L, Mitchell BD, Mahaney MC, Dyer TD, Stern MP, MacCluer JW, Blangero J 1997 A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nat Genet 15:273-276
7. Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V, Vaillant E, Lorentz N, Basdevant A, Clement K, Guy-Grand B, Froguel P 1998 A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet 20:304-308
8. Rotimi CN, Comuzzie AG, Lowe WL, Luke A, Blangero J, Cooper RS 1999 The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans. Diabetes 48:643-644
9. Hixson JE, Almasy L, Cole S, Birnbaum S, Mitchell BD, Mahaney MC, Stern MP, MacCluer JW, Blangero J, Comuzzie AG 1999 Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC. J Clin Endocrinol Metab 84:3187-3191
10. Carroll L, Voisey J, van Daal A 2005 Gene polymorphisms and their effects in the melanocortin system. Peptides 26:1871-1885
11. Hinney A, Becker I, Heibult O, Nottebom K, Schmidt A, Ziegler A, Mayer H, Siegfried W, Blum WF, Remschmidt H, Hebebrand J 1998 Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes. J Clin Endocrinol Metab 83:3737-3741
12. Biebermann H, Castaneda TR, van Landeghem F, von Deimling A, Escher F, Brabant G, Hebebrand J, Hinney A, Tschop MH, Gruters A, Krude H 2006 A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab 3:141-146
13. Echwald SM, Sorensen TI, Andersen T, Tybjaerg-Hansen A, Clausen JO, Pedersen O 1999 Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity. Int J Obes Relat Metab Disord 23:293-298
14. Suviolahti E, Ridderstrale M, Almgren P, Klannemark M, Melander O, Carlsson E, Carlsson M, Hedenbro J, Orho-Melander M 2003 Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals. Int J Obes Relat Metab Disord 27:1204-1211
15. Miraglia del Giudice E, Cirillo G, Santoro N, D'Urso L, Carbone MT, Di Toro R, Perrone L 2001 Molecular screening of the proopiomelanocortin (POMC) gene in Italian obese children: report of three new mutations. Int J Obes Relat Metab Disord 25:61-67
16. Buono P, Pasanisi F, Nardelli C, Ieno L, Capone S, Liguori R, Finelli C, Oriani G, Contaldo F, Sacchetti L 2005 Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes in severely obese adults living in southern Italy. Clin Chem 51:1358-1364
17. Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O'Rahilly S 2002 A missense mutation disrupting a dibasic prohormone processing site in proopiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 11:1997-2004
18. Lee YS, Challis BG, Thompson DA, Yeo GS, Keogh JM, Madonna ME, Wraight V, Sims M, Vatin V, Meyre D, Shield J, Burren C, Ibrahim Z, Cheetham T, Swift P, Blackwood A, Hung CC, Wareham NJ, Froguel P, Millhauser GL, O'Rahilly S, Farooqi IS 2006 A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance. Cell Metab 3:135-140
19. Delplanque J, Barat-Houari M, Dina C, Gallina P, Clement K, Guy-Grand B, Vasseur F, Boutin P, Froguel P 2000 Linkage and association studies between the proopiomelanocortin (POMC) gene and obesity in Caucasian families. Diabetologia 43:1554-1557
20. Dubern B, Clement K, Pelloux V, Froguel P, Girardet JP, Guy-Grand B, Tounian P 2001 Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J Pediatr 139:204-209
21. Rolland-Cachera MF, Cole TJ, Sempe M, Tichet J, Rossignol C, Charraud A 1991 Body mass index variations: centiles from birth to 87 years. Eur J Clin Nutr 45:13-21
22. Simon C, Wagner A, DiVita C, Rauscher E, Klein-Platat C, Arveiler D, Schweitzer B, Triby E 2004 Intervention centred on adolescents' physical activity and sedentary behaviour (ICAPS): concept and 6-month results. Int J Obes Relat Metab Disord 28:S96-S103
23. Lubrano-Berthelier C, Durand E, Dubern B, Shapiro A, Dazin P, Weill J, Ferron C, Froguel P, Vaisse C 2003 Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Hum Mol Genet 12:145-153
24. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398-401
25. Bertagna X, Lenne F, Comar D, Massias JF, Wajcman H, Baudin V, Luton JP, Girard F 1986 Human beta-melanocyte-stimulating hormone revisited. Proc Natl Acad Sci U S A 83:9719-9723
26. Harrold JA, Williams G 2006 Melanocortin-4 receptors, beta-MSH and leptin: key elements in the satiety pathway. Peptides 27:365-371
27. Lubrano-Berthelier C, Dubern B, Lacorte JM, Picard F, Shapiro A, Zhang S, Bertrais S, Hercberg S, Basdevant A, Clement K, Vaisse C 2006 Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab 91:1811-1818
28. Hinney A, Bettecken T, Tarnow P, Brumm H, Reichwald K, Lichtner P, Scherag A, Nguyen TT, Schlumberger P, Rief W, Vollmert C, Illig T, Wichmann HE, Schafer H, Platzer M, Biebermann H, Meitinger T, Hebebrand J 2006 Prevalence, spectrum, and functional characterization of melanocortin-4 receptor gene mutations in a representative population-based sample and obese adults from Germany. J Clin Endocrinol Metab 91:1761-1769