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Proopiomelanocortin (POMC) sequencing and developmental delay: Preliminary evidence for a SNP in the 3’ UTR region of the POMC gene—Possible relevance for biological risk and self-injurious behavior

Published online by Cambridge University Press:  16 July 2018

John A. Damerow ,
Raymond C. Tervo ,
Michael Ehrhardt ,
Angela Panoskaltsis-Mortari  and
Frank J. Symons
John A. Damerow
Affiliation:
University of Minnesota
Raymond C. Tervo
Affiliation:
Mayo Clinic Gillette Children's Specialty Healthcare
Michael Ehrhardt
Affiliation:
University of Minnesota
Angela Panoskaltsis-Mortari
Affiliation:
University of Minnesota
Frank J. Symons*
Affiliation:
University of Minnesota
*
Address correspondence and reprint requests to: Frank Symons, Department of Educational Psychology, Educational Sciences Building, 56 River Road, College of Education and Human Development, University of Minnesota, Minneapolis, MN 55455; E-mail: [email protected].
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Abstract

The proopiomelanocortin (POMC) molecule has been implicated in models of self-injurious behavior (SIB) in neurodevelopmental disorders, but it has never been specifically sequenced in search of base specific polymorphisms. The empirical focus of this preliminary study was to sequence the POMC gene in 11 children (mean age = 41.8 months, range = 12–60 months; 73% male) with clinical concerns regarding global developmental delay, 5 with reported self-injury. Genomic DNA was extracted from blood samples, and the POMC gene was amplified by specific oligonucleotide primers via polymerase chain reaction. The amplified gene products were sequenced by the University of Minnesota Genomic Center, and the results were analyzed using Sequencher software. A single nucleotide polymorphism (SNP), 1130 C>T, was found in the 3’ untranslated region (UTR) of two samples (one of whom had SIB). The program TargetScanHuman was used to predict the function of this mutation. Variant c.1130 C<T was predicted to be located in the target site of two microRNAs (miRNAs; hsa-mir-3715 and hsa-mir-1909), and the variant allele T may result in an increased minimum free energy for the two miRNAs. Further work with much larger samples is needed to continue the investigation of POMC’s possible function as a risk factor for the development of SIB in children with developmental delay/disability. The findings presented in this study show that the SNP found in the 3’ UTR could alter the binding of miRNAs to POMC 3'UTR, thus, increasing POMC expression and affecting several biological systems with high relevance to the biology of self-injury. There was a significant difference in β-endorphin levels between SIB (M = 169.25 pg/mL) and no SIB (M = 273.5 pg/mL, SD = 15.2) cases (p < .01). Intervention implications are tied to prior observations of individual differences among SIB responders and nonresponders to treatment with the opioid antagonist naltrexone. Stratifying individuals with SIB by POMC mutation status may provide a potential tailoring-like variable to guide the selection of who is more (or less) likely to respond to opiate antagonist treatment. Currently, opioid antagonistic treatment for SIB is empiric (trial and error).

Type
Regular Articles
Information
Development and Psychopathology , Volume 31 , Issue 2 , May 2019 , pp. 433 - 438
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

Supported, in part, by NICHD Grant No. 44763, 47201. Our sincere thanks to Kent M. Reed and Kristelle M. Mendoza for their bench assistance throughout this project and to Chantel Barney for specimen procurement and the children and their families for their support.

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