title: Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity.
abstract: BACKGROUND
  Melanocortin-4-receptor (MC4R) mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype.
  
  
  METHODS
  To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index > or = 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese), obesity onset before the 10 years old, height > or = 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 +/- 3.1, mean BMI 30.8 +/- 5.4) and in 200 controls (mean age 8.1 +/- 2.8; mean BMI 14.2 +/- 2.5).
  
  
  RESULTS
  Three mutations have been found in five obese children. The S127L (C380T), found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showed that only Q307X impaired protein function.
  
  
  CONCLUSIONS
  The low prevalence of MC4R mutations (1.6%) in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.
authors.affiliation: Dipartimento di Pediatria F, Fede, Seconda Università degli Studi di Napoli, Napoli, Italy. nicolasantoro@hotmail.com
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Grazia
authors.initials: G
authors.lastname: Cirillo
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xiang
authors.forename: Rita
authors.initials: R
authors.lastname: Tanas
authors.forename: Nella
authors.initials: N
authors.lastname: Greggio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iughetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vottero
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salvatoni
authors.forename: Mario
authors.initials: M
authors.lastname: Di Pietro
authors.forename: Antonio
authors.initials: A
authors.lastname: Balsamo
authors.forename: Antonino
authors.initials: A
authors.lastname: Crinò
authors.forename: Anna
authors.initials: A
authors.lastname: Grandone
authors.forename: Carrie
authors.initials: C
authors.lastname: Haskell-Luevano
authors.forename: Laura
authors.initials: L
authors.lastname: Perrone
authors.forename: Emanuele Miraglia
authors.initials: EM
authors.lastname: del Giudice
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D019943:Amino Acid Substitution; D001827:Body Height; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4