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Case Reports
. 2019 Sep;27(9):1475-1480.
doi: 10.1038/s41431-019-0430-5. Epub 2019 May 31.

Microdeletion of pseudogene chr14.232.a affects LRFN5 expression in cells of a patient with autism spectrum disorder

Gerarda Cappuccio  1   2 , Sergio Attanasio  2 , Marianna Alagia  1 , Margherita Mutarelli  2 , Roberta Borzone  2 , Marianthi Karali  2   3 , Rita Genesio  4 , Angela Mormile  4 , Lucio Nitsch  4 , Floriana Imperati  1 , Annalisa Esposito  1 , Sandro Banfi  2   3 , Ennio Del Giudice  1 , Nicola Brunetti-Pierri  5   6
Affiliations
Case Reports

Microdeletion of pseudogene chr14.232.a affects LRFN5 expression in cells of a patient with autism spectrum disorder

Gerarda Cappuccio et al. Eur J Hum Genet. 2019 Sep.

Abstract

We identified a 14q21.2 microdeletion in a 16-year-old boy with autism spectrum disorder (ASD), IQ in the lower part of normal range but high-functioning memory skills. The deletion affects a gene desert, and the non-deleted gene closest to the microdeletion boundaries is LRFN5, which encodes a protein involved in synaptic plasticity and implicated in neuro-psychiatric disorders. LRFN5 expression was significantly decreased in the proband's skin fibroblasts. The deleted region includes the pseudogene chr14.232.a, which is transcribed into a long non-coding RNA (lncLRFN5-10), whose levels were also significantly reduced in the proband's fibroblasts compared to controls. Transfection of the patient's fibroblasts with a plasmid expressing chr14.232.a significantly increased LRFN5 expression, while siRNA targeting chr14.232.a-derived lncLRFN5-10 reduced LRFN5 levels. In summary, we report on an individual with ASD carrying a microdeletion encompassing the pseudogene chr14.232.a encoding for lncLRFN5-10, which was found to affect the expression levels of the nearby, non-deleted LRFN5. This case illustrates the potential role of long non-coding RNAs in regulating expression of neighbouring genes with a functional role in ASD pathogenesis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Microdeletion at 14q21.2 (chr14:43545282-43837068 according to hg19), detected in the proband, is highlighted in yellow, whereas LRFN5 (chr14:42076764-42373752), at 1.12 Mb distance, is highlighted in the light blue area. b Expression levels of LRFN5 in the proband (P), his father (F) and controls (CTRLs) (n = 7) were significantly reduced in the proband and his father (**p < 0.001, *p < 0.005). c Expression levels of chr14.232.a in the proband (P), his father (F) and controls (CTRLs) (n = 5) were significantly reduced in the proband (*p < 0.05)
Fig. 2
Fig. 2
a Expression levels of chr14.232.a were increased following transfection of a plasmid expressing chr14.232.a in the proband’s skin fibroblasts. (*p < 0.05) b LRFN5 expression levels were significantly increased after chr14.232.a transfection in the proband’s skin fibroblasts. (*p < 0.05). c SiRNA knock-down of chr14.232.a decreased chr14.232.a expression in control fibroblasts (n = 5) (*p < 0.05). d LRFN5 expression levels were significantly reduced after transfection of siRNA targeting chr14.232.a in control fibroblasts (n = 5) (*p < 0.05)
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