Childhood obesity became a global plague: 9% of Italian children (17% of USA children) is obese and 21% is overweight. Nowadays only a small number of obese children undergoes genetic analysis, usually when obesity is associated with dysmorphic features. Our purpose was to identify genomic rearrangement causing obesity: we analyzed the DNA of 52 children by array-CGH (platform CytoScan-HD, Affymetrix). Patients included in our study were 29 males (55,8%) and 23 females (44,2%) obese, they presented dysmorphic features and/or mental retardation, hyperphagia and the improvement of the nutritional approach was not having any benefit reducing their weight. The average BMI was 28.42 kg/m 2 (SDS 2.64). 24 patients (46,15%) resulted positive on array-CGH analysis (33,4% females, 66,6% males); among these patients 41,2% presented dysmorphic features and 50% were affected by mental retardation. In 8 patients with a genetic rearrangement this was related to obesity and in 1 patient the link was suspected but not proved. Genetic rearrangements identified that can be causative of obesity are 4 deletions and 4 duplications. Del16p11.2 (813kb e 232kb) are described in association with obesity in childhood; dupXp22.31(1,6Mb) (genes HDHD1, STS, VCX, PNPLA4) causes over-expression of PNPLA4, that has been related to obesity. Genetic rearrangements of single genes are two dup18q(393 kb) and one del7q21.3(55kb), involving respectively genes ONECUT2 and BAIAP2L1, coding for molecules part of insulin pattern signaling. Dup3q24q25.1(180kb) and del20q13.13(109kb) code for CP and STAU1: among obese patients have been described mutations of these two genes but their pathogenetic role has not be clarified yet. Del6q21(33kb) involves gene LAMA4: this rearrangement has an undefined meaning; in animal models LAMA4 seems to have a function in development of fatty tissue but in humans this function is not known yet. 46,15 % of patients of our cohort presented array-CGH positive for genomic rearrangements and this data justifies the execution of genetic analysis in obese children presenting dysmorphic features and/or mental retardation. 33,3% of our patients resulted positive on array-CGH analysis in absence of dysmorphic features and/or mental retardation, so genomic analysis could have an important role either in obese patients without syndromic features. We can affirm that in obese children array-CGH analysis could help in identification of causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.

Obesity in pediatric age: The analysis of genomic rearrangements / Filomena Madeo, Simona; Ciancia, Silvia; Leo, Francesco; Bruzzi, Patrizia; Predieri, Barbara; Stanghellini, Ilaria; Calabrese, Olga; Iughetti, Lorenzo. - In: HORMONE RESEARCH IN PAEDIATRICS. - ISSN 1663-2818. - 91:suppl 1(2019), pp. 119-120. ((Intervento presentato al convegno 58th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE) tenutosi a Vienna nel September 19–21, 2019.

Obesity in pediatric age: The analysis of genomic rearrangements

Silvia Ciancia;Francesco Leo;Barbara Predieri;Ilaria Stanghellini;Olga Calabrese;Lorenzo Iughetti
2019

Abstract

Childhood obesity became a global plague: 9% of Italian children (17% of USA children) is obese and 21% is overweight. Nowadays only a small number of obese children undergoes genetic analysis, usually when obesity is associated with dysmorphic features. Our purpose was to identify genomic rearrangement causing obesity: we analyzed the DNA of 52 children by array-CGH (platform CytoScan-HD, Affymetrix). Patients included in our study were 29 males (55,8%) and 23 females (44,2%) obese, they presented dysmorphic features and/or mental retardation, hyperphagia and the improvement of the nutritional approach was not having any benefit reducing their weight. The average BMI was 28.42 kg/m 2 (SDS 2.64). 24 patients (46,15%) resulted positive on array-CGH analysis (33,4% females, 66,6% males); among these patients 41,2% presented dysmorphic features and 50% were affected by mental retardation. In 8 patients with a genetic rearrangement this was related to obesity and in 1 patient the link was suspected but not proved. Genetic rearrangements identified that can be causative of obesity are 4 deletions and 4 duplications. Del16p11.2 (813kb e 232kb) are described in association with obesity in childhood; dupXp22.31(1,6Mb) (genes HDHD1, STS, VCX, PNPLA4) causes over-expression of PNPLA4, that has been related to obesity. Genetic rearrangements of single genes are two dup18q(393 kb) and one del7q21.3(55kb), involving respectively genes ONECUT2 and BAIAP2L1, coding for molecules part of insulin pattern signaling. Dup3q24q25.1(180kb) and del20q13.13(109kb) code for CP and STAU1: among obese patients have been described mutations of these two genes but their pathogenetic role has not be clarified yet. Del6q21(33kb) involves gene LAMA4: this rearrangement has an undefined meaning; in animal models LAMA4 seems to have a function in development of fatty tissue but in humans this function is not known yet. 46,15 % of patients of our cohort presented array-CGH positive for genomic rearrangements and this data justifies the execution of genetic analysis in obese children presenting dysmorphic features and/or mental retardation. 33,3% of our patients resulted positive on array-CGH analysis in absence of dysmorphic features and/or mental retardation, so genomic analysis could have an important role either in obese patients without syndromic features. We can affirm that in obese children array-CGH analysis could help in identification of causative genetic mutations, with consequent advantage in therapeutic management and follow-up of these patients.
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Filomena Madeo, Simona; Ciancia, Silvia; Leo, Francesco; Bruzzi, Patrizia; Predieri, Barbara; Stanghellini, Ilaria; Calabrese, Olga; Iughetti, Lorenzo
Obesity in pediatric age: The analysis of genomic rearrangements / Filomena Madeo, Simona; Ciancia, Silvia; Leo, Francesco; Bruzzi, Patrizia; Predieri, Barbara; Stanghellini, Ilaria; Calabrese, Olga; Iughetti, Lorenzo. - In: HORMONE RESEARCH IN PAEDIATRICS. - ISSN 1663-2818. - 91:suppl 1(2019), pp. 119-120. ((Intervento presentato al convegno 58th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE) tenutosi a Vienna nel September 19–21, 2019.
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