Please cite this article as follows: Agranat Meged A, Ghanadri Y, Eisenberg I, Ben Neriah Z, Kieselstein-Gross E, Mitrani-Rosenbaum S. 2008. Attention Deficit Hyperactivity Disorder in Obese Melanocortin-4-Receptor (MC4R) Deficient Subjects: A Newly Described Expression of MC4R Deficiency. Am J Med Genet Part B 147B:1547–1553.
Attention deficit hyperactivity disorder in obese melanocortin-4-receptor (MC4R) deficient subjects: A newly described expression of MC4R deficiency†
Article first published online: 5 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Special Issue: Special Issue on the Genetics of ADHD Dedicated to the Memory of Richard Todd
Volume 147B, Issue 8, pages 1547–1553, 5 December 2008
How to Cite
Agranat-Meged, A., Ghanadri, Y., Eisenberg, I., Ben Neriah, Z., Kieselstein-Gross, E. and Mitrani-Rosenbaum, S. (2008), Attention deficit hyperactivity disorder in obese melanocortin-4-receptor (MC4R) deficient subjects: A newly described expression of MC4R deficiency. Am. J. Med. Genet., 147B: 1547–1553. doi: 10.1002/ajmg.b.30842
- Issue published online: 18 NOV 2008
- Article first published online: 5 SEP 2008
- Manuscript Accepted: 8 JUL 2008
- Manuscript Received: 14 APR 2008
- attention deficit hyperactivity disorder;
- genetics behavioral;
Attention deficit hyperactivity disorder (ADHD) is a heterogeneous highly heritable disorder which has recently been described to be comorbid in obese subjects. This study investigated phenotype/genotype associations in a consanguineous family with genetic obesity due to the melanocortin-4-receptor (MC4R) (C271R) mutation. MC4R deficiency disrupts hunger/satiety regulation resulting in abnormal eating behaviors. To date, the behavioral/psychiatric characteristics of MC4R deficiency have not been described except for a possible association with Binge Eating Disorder. Twenty-nine subjects of a family known to carry the MC4R (C271R) mutation, were genotyped for the mutation and underwent extensive evaluations in search for physical/psychiatric phenotype characteristics. Subjects originated from proband nuclear families with morbid obese children (BMI percentile > 97%). All probands were homozygous for the MC4R (C271R) mutation. ADHD prevalence was higher than expected only in the groups carrying the homozygous or heterozygous mutation (P = 0.00057, 0.0028, respectively). An obvious difference was observed between the homozygous group and the rest of the family in terms of obesity: homozygous subjects had childhood morbid obesity whereas heterozygous subjects included lean, normal weight and later onset obese subjects. A significant difference was found in ADHD prevalence between the homozygous MC4R (C271R) group (80%) and the rest of the family (22%) (P = 0.033) and a significant trend was found between ADHD prevalence and the number of MC4R (C271R) alleles (P = 0.0267). We conclude that in our sample, the MC4R (C271R) mutation causing obesity, is in association with ADHD. Identifying specific subgroups in which the comorbidity of obesity and ADHD occur may contribute to the understanding of the underlying molecular mechanisms. © 2008 Wiley-Liss, Inc.