Identification of two novel loss-of-function SIM1 mutations in two overweight children with developmental delay.
Obesity (Silver Spring)
; 22(12): 2621-4, 2014 Dec.
Article
in En
| MEDLINE
| ID: mdl-25234154
ABSTRACT
OBJECTIVE:
Several deletions of chromosome 6q, including SIM1, were reported in obese patients with developmental delay. Furthermore, rare loss-of-function SIM1 mutations were shown to contribute to severe obesity, yet the role of these mutations in developmental delay remained unclear. Here, SIM1 in children with neurodevelopmental abnormalities was screened and the functional effect of the identified mutations was investigated.METHODS:
SIM1 was sequenced in 283 children presenting with developmental delay and at least overweight. The effect of the identified mutations on SIM1 transcriptional activity in stable human cell lines was assessed using luciferase gene reporter assays.RESULTS:
Two novel mutations (c.886A>G/p.R296G and c.925A>G/p.S309G) in two boys with variable degrees of cognitive deficits and weight issues were identified. The child mutated for p.R296G presented with a generally more severe phenotype than the p.S309G carrier (obesity, compulsive eating, neonatal hypotonia versus overweight only), while both mutations had strong loss-of-function effects on SIM1 transcriptional activity.CONCLUSIONS:
Severe loss-of-function SIM1 mutations can be associated with a spectrum of developmental delay phenotypes and obesity. Our data suggest that SIM1 sequencing should be performed more systematically in patients with developmental delay, even in the absence of severe obesity. These results deserve further SIM1 screening studies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Obesity, Morbid
/
Developmental Disabilities
/
Basic Helix-Loop-Helix Transcription Factors
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Obesity (Silver Spring)
Journal subject:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Year:
2014
Type:
Article
Affiliation country:
France