Microdeletion of pseudogene chr14.232.a affects LRFN5 expression in cells of a patient with autism spectrum disorder.
Eur J Hum Genet
; 27(9): 1475-1480, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31152157
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomes, Human, Pair 14
/
Membrane Glycoproteins
/
Pseudogenes
/
Gene Expression
/
Chromosome Deletion
/
Autism Spectrum Disorder
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Humans
/
Male
Language:
En
Journal:
Eur J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2019
Document type:
Article
Affiliation country:
Italy