Biochemical and Biophysical Research Communications
Mutations in the gene encoding CADM1 are associated with autism spectrum disorder
Section snippets
Materials and methods
Patients. We obtained the DNA of 195 Caucasian patients, 170 males and 25 females, from the Autism Genetic Resource Exchange (AGRE) Consortium (Cure Autism Now, Los Angels, CA). All samples were from familial cases of Autism Spectrum Disorder (ASD) or Pervasive Developmental Disorder—not otherwise specified (PDD-nos). Caucasian control samples were obtained from the Coriell Institute (Camden, NJ). The study was approved by the Committee of Ethics at Jichi Medical University.
PCR amplification.
Results
We screened mutations in the CADM1 gene of Caucasian DNA samples from the Autism Genetic Resource Exchange (AGRE) Consortium and detected two missense mutations, C739A (H246N) and A755C (Y251S), in the CADM1 gene of male patients AU014803 and AU078704, respectively (Fig. 1A). These mutations were located in the third immunoglobulin (Ig3) domain (Fig. 1B), which is essential for homophilic or heterophilic transactive interaction [8]. However, these mutations were not detected in 197 control
The relationship between the mutation of CADM1 and the pathogenesis of ASD
The prevalence of CADM1 mutations in the DNA samples evaluated in this study is reasonable considering the prevalence of NLGN mutations in Autism patients; three percent have missense mutations in the conserved region of NLGN4, but no changes in NLGN3 [13]. The H246N and Y251S mutations were also detected in the other affected members of these two families (Fig. 2). In addition to the affected patients, however, mutations were detected in the non-manifesting sister (AU014804) and mother
Acknowledgments
We express our deepest sympathy at the untimely passing of an excellent neuroscientist, Dr. El-Husseini A. This work was supported by the Ministry of Education Science, and Sport research Grant (18700333, 19790739, 19500305). We gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Autism Speaks and is supported, in part, by grant 1U24MH081810 from the
References (21)
- et al.
Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons
Cell
(2000) - et al.
Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins
Cell
(2004) - et al.
Contribution of SHANK3 mutations to autism spectrum disorder
Am. J. Hum. Genet.
(2007) - et al.
RA175, which is the mouse ortholog of TSLC1, a tumor suppressor gene in human lung cancer, is a cell adhesion molecule
Exp. Cell Res.
(2003) - et al.
Rapid and efficient site-specific mutagenesis without phenotypic selection
Methods Enzymol.
(1987) - et al.
Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ ADAM17-like proteases
Neurosci. Lett.
(2008) - et al.
The neuropathology of autism
J. Neuropathol. Exp. Neurol.
(2005) - et al.
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Nat. Genet.
(2003) - et al.
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders
Nat. Genet.
(2007) - et al.
Expression of RA175 mRNA, a new member of the immunoglobulin superfamily, in developing mouse brain
Neuroreport
(2001)
Cited by (82)
Nectins and Nectin-like molecules in synapse formation and involvement in neurological diseases
2021, Molecular and Cellular NeuroscienceCitation Excerpt :Necl-1 expression is significantly upregulated in pyroglutamate-modified amyloid β-expressing transgenic mice (TBA42 mice) (Yang et al., 2013), suggesting that Necl-1 is implicated in the pathology of Alzheimer's disease. The NECL-2/CADM1 gene is genetically associated with autism, depression, and suicidality (Kitagishi et al., 2015; Niculescu et al., 2015; Redei et al., 2014; Zhiling et al., 2008). In addition, disruption of Necl-2-dependent astroglial function results in behavioral abnormalities, which are similar to those described in the animal model of attention-deficit/hyperactivity disorder (Sandau et al., 2012).
Changes in brain synapse-related molecules with age
2021, Factors Affecting Neurological Aging: Genetics, Neurology, Behavior, and DietSynaptic recognition molecules in development and disease
2021, Current Topics in Developmental BiologyRepint of “Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity”
2018, Neuroscience and Biobehavioral ReviewsReframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity
2017, Neuroscience and Biobehavioral ReviewsSynCAMs – From axon guidance to neurodevelopmental disorders
2017, Molecular and Cellular Neuroscience
- 1
These authors contributed equally this work.