Gene expression analysis in lymphoblasts derived from patients with autism spectrum disorder

Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita, 565-0871, Osaka, Japan. .
Molecular Autism (Impact Factor: 5.41). 05/2011; 2(1):9. DOI: 10.1186/2040-2392-2-9
Source: PubMed


The autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that result in severe and pervasive impairment in the development of reciprocal social interaction and verbal and nonverbal communication skills. In addition, individuals with ASD have stereotypical behavior, interests and activities. Rare mutations of some genes, such as neuroligin (NLGN) 3/4, neurexin (NRXN) 1, SHANK3, MeCP2 and NHE9, have been reported to be associated with ASD. In the present study, we investigated whether alterations in mRNA expression levels of these genes could be found in lymphoblastoid cell lines derived from patients with ASD.
We measured mRNA expression levels of NLGN3/4, NRXN1, SHANK3, MeCP2, NHE9 and AKT1 in lymphoblastoid cells from 35 patients with ASD and 35 healthy controls, as well as from 45 patients with schizophrenia and 45 healthy controls, using real-time quantitative reverse transcriptase polymerase chain reaction assays.
The mRNA expression levels of NLGN3 and SHANK3 normalized by β-actin or TBP were significantly decreased in the individuals with ASD compared to controls, whereas no difference was found in the mRNA expression level of MeCP2, NHE9 or AKT1. However, normalized NLGN3 and SHANK3 gene expression levels were not altered in patients with schizophrenia, and expression levels of NLGN4 and NRXN1 mRNA were not quantitatively measurable in lymphoblastoid cells.
Our results provide evidence that the NLGN3 and SHANK3 genes may be differentially expressed in lymphoblastoid cell lines from individuals with ASD compared to those from controls. These findings suggest the possibility that decreased mRNA expression levels of these genes might be involved in the pathophysiology of ASD in a substantial population of ASD patients.

Download full-text


Available from: Kazutaka Ohi,
15 Reads
  • Source
    • "The patients were diagnosed by at least two trained child psychiatrists and/or child neurologists according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The assessments were performed using unstructured or semi-structured behavioral observation and interviews with the patients and their parents or caregivers [16]. Additionally, the participants met the ASD criteria of the Autism Diagnostic Interview-Revised (ADI-R) [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication.
    Annals of General Psychiatry 08/2014; 13(1):22. DOI:10.1186/s12991-014-0022-2 · 1.40 Impact Factor
  • Source
    • "Interestingly, Shank3 protein interacts with both PSD-95 and Neuroligins . Recently, mutations in Shank3 have been linked to ASD (Yasuda et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Very often, developmental abnormalities or subtle disturbances of neuronal function may yield brain diseases even if they become obvious only late in life. It is therefore our intention to highlight fundamental mechanisms of neuronal cell biology with a special emphasis on dendritic mRNA localization including local protein synthesis at the activated synapse. Furthermore, we would like to point out possible links to neuronal or synaptic dysfunction. In particular, we will focus on a series of well-known RNA-binding proteins that are involved in these processes and outline how their dysfunction might yield neurodevelopmental, neurodegenerative or neuropsychiatric disorders. We are convinced that increasing our understanding of RNA biology in general and the mechanisms underlying mRNA transport and subsequent translation at the synapse will ultimately generate important novel RNA-based tools in the near future that will allow us to hopefully treat some of these devastating diseases.
    European Journal of Neuroscience 06/2012; 35(12):1818-36. DOI:10.1111/j.1460-9568.2012.08160.x · 3.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: On March 9, 1862 the ironclad warships USS Monitor and CSS Virginia (ex-USS Merrimack) fought to a draw at Hampton Roads, Virginia, in one of the most recognized sea battles in history. Now, 135 years later, the Monitor is fighting a losing battle against both natural and human threats. The Monitor's hull, lying in 230 ft. (71 m) of water off Cape Hatteras, North Carolina, is deteriorating at an alarming rate. The National Oceanic and Atmospheric Administration (NOAA) is responsible for the Monitor which, in 1975, was designated America's first National Marine Sanctuary. As a result, NOAA is aggressively applying comprehensive planning strategy and ocean technology to the problem of protecting the Monitor
    OCEANS '97. MTS/IEEE Conference Proceedings; 11/1997
Show more