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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2009

Open Access 01-12-2009 | Research article

Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

Authors: Nicola Santoro, Grazia Cirillo, Zhimin Xiang, Rita Tanas, Nella Greggio, Giuseppe Morino, Lorenzo Iughetti, Alessandra Vottero, Alessandro Salvatoni, Mario Di Pietro, Antonio Balsamo, Antonino Crinò, Anna Grandone, Carrie Haskell-Luevano, Laura Perrone, Emanuele Miraglia del Giudice

Published in: BMC Medical Genetics | Issue 1/2009

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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 ≥ 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 ≥ 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.

Conclusion

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.
Appendix
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Metadata
Title
Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity
Authors
Nicola Santoro
Grazia Cirillo
Zhimin Xiang
Rita Tanas
Nella Greggio
Giuseppe Morino
Lorenzo Iughetti
Alessandra Vottero
Alessandro Salvatoni
Mario Di Pietro
Antonio Balsamo
Antonino Crinò
Anna Grandone
Carrie Haskell-Luevano
Laura Perrone
Emanuele Miraglia del Giudice
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2009
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-10-25

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