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Clinical Research Group, Department of Child and Adolescent Psychiatry (A.H., I.B., O.H.; K.N., A.S., H.R., J.H.), University of Marburg, Hans-Sachs-Str. 6, 35033 Marburg, FRG; Institute of Medical Biometry and Epidemiology (A.Z.), University of Marburg; Marburg, FRG; Children’s Hospital Hochried (H.M.), Murnau, FRG; Obesity Treatment Center Insula (W.S.), Berchtesgaden, FRG; Children’s Hospital (W.F.B.), University of Giessen, FRG; Lilly Germany (W.F.B.), Bad Homburg, FRG.
Abstract
Pro-opiomelanocortin (POMC) is the precursor of melanocortins
(adrenocorticotropin: ACTH, ß-endorphin, ß-lipotropin; ß-LPH
corticotropin like intermediate peptide, 
-, ß- and
-melanocyte-stimulating hormone: -, ß- and -MSH) some of
which act in the brain to reduce food intake and are potential
mediators of leptin action. Recently, three different mutations in the
POMC gene (POMC) were identified in two unrelated children
that lead to early-onset extreme obesity, adrenal insufficiency, and
red hair pigmentation (1). In the present study we systematically
screened the coding region of POMC in 96 extremely obese
children and adolescents, 60 healthy underweight individuals and 46
patients with anorexia nervosa (AN) and identified several variants. a)
A 9 and an 18 base pair insertion (9bp and 18bp: AGC AGC GGC and AGC
AGC GGC AGC AGC GGC, respectively, between codon 73 and 74; 1,2). These
in-frame variants lead to the insertion of three or six amino acids
(Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal to -MSH.
Frequencies of the 9bp insertion allele varied between 3 and 5% among
the different study groups (Pearson’s 
2 P>0.5). b)
Both an out-of-frame 6 bp insertion (within codon 176: GGG CCC) leading
to the insertion of two amino acids (Arg-Ala) and a premature
stop-codon (G-7316-T: Glu-180-Stop) within the -LPH sequence were
maternally inherited in an obese female proband. This proband inherited
another missense mutation from her father (Glu-188-Gly). c) A missense
mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with
AN who also harboured the 9bp insertion on a paternally derived
haplotype. d) The allelic co-occurence of two silent mutations
(C-6982-T and C-7285-T) was detected in two obese subjects. e) Two
further silent mutations (C-3832-T; C-7111-G) were detected in an
underweight and an obese subject, respectively. We conclude that the
POMC gene harbors several different polymorphisms and mutations, none
of which can readily be associated with the phenotypes under study.
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