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author:("Smith, mora")
1.  Mitochondrial and Ion Channel Gene Alterations in Autism 
Biochimica et biophysica acta  2012;1817(10):1796-1802.
To evaluate the potential importance in autistic subjects of copy number variants (CNVs) that alter genes of relevance to bioenergetics, ionic metabolism, and synaptic function, we conducted a detailed microarray analysis of 69 autism probands and 35 parents, compared to 89 CEU HapMap controls. This revealed that the frequency CNVs of ≥ 100 kb and CNVs of ≥ 10 Kb were markedly increased in probands over parents and in probands and parents over controls. Evaluation of CNVs ≥ 1 Mb by chromosomal FISH confirmed the molecular identity of a subset of the CNVs, some of which were associated with chromosomal rearrangements. In a number of the cases, CNVs were found to alter the copy number of genes that are important in mitochondrial oxidative phosphorylation (OXPHOS), ion and especially calcium transport, and synaptic structure. Hence, autism might result from alterations in multiple bioenergetic and metabolic genes required for mental function.
PMCID: PMC3423964  PMID: 22538295
autism; mitochondria; OXPHOS; copy number variants (CNVs); calcium channels; synapses
2.  A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R 
BMC Medical Genetics  2004;5:10.
Autism is a pervasive developmental disorder characterized by a triad of deficits: qualitative impairments in social interactions, communication deficits, and repetitive and stereotyped patterns of behavior. Although autism is etiologically heterogeneous, family and twin studies have established a definite genetic basis. The inheritance of idiopathic autism is presumed to be complex, with many genes involved; environmental factors are also possibly contributory. The analysis of chromosome abnormalities associated with autism contributes greatly to the identification of autism candidate genes.
Case presentation
We describe a child with autistic disorder and an interstitial deletion on chromosome 4q. This child first presented at 12 months of age with developmental delay and minor dysmorphic features. At 4 years of age a diagnosis of Pervasive Developmental Disorder was made. At 11 years of age he met diagnostic criteria for autism. Cytogenetic studies revealed a chromosome 4q deletion. The karyotype was 46, XY del 4 (q31.3-q33). Here we report the clinical phenotype of the child and the molecular characterization of the deletion using molecular cytogenetic techniques and analysis of polymorphic markers. These studies revealed a 19 megabase deletion spanning 4q32 to 4q34. Analysis of existing polymorphic markers and new markers developed in this study revealed that the deletion arose on a paternally derived chromosome. To date 33 genes of known or inferred function are deleted as a consequence of the deletion. Among these are the AMPA 2 gene that encodes the glutamate receptor GluR2 sub-unit, GLRA3 and GLRB genes that encode glycine receptor subunits and neuropeptide Y receptor genes NPY1R and NPY5R.
The deletion in this autistic subject serves to highlight specific autism candidate genes. He is hemizygous for AMPA 2, GLRA3, GLRB, NPY1R and NPY5R. GluR2 is the major determinant of AMPA receptor structure. Glutamate receptors maintain structural and functional plasticity of synapses. Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory. Glycine receptors are expressed in very early cortical development. Molecular cytogenetic studies and DNA sequence analysis in other patients with autism will be necessary to confirm that these genes are involved in autism.
PMCID: PMC411038  PMID: 15090072
3.  Mapping autism risk loci using genetic linkage and chromosomal rearrangements 
Szatmari, Peter | Paterson, Andrew | Zwaigenbaum, Lonnie | Roberts, Wendy | Brian, Jessica | Liu, Xiao-Qing | Vincent, John | Skaug, Jennifer | Thompson, Ann | Senman, Lili | Feuk, Lars | Qian, Cheng | Bryson, Susan | Jones, Marshall | Marshall, Christian | Scherer, Stephen | Vieland, Veronica | Bartlett, Christopher | Mangin, La Vonne | Goedken, Rhinda | Segre, Alberto | Pericak-Vance, Margaret | Cuccaro, Michael | Gilbert, John | Wright, Harry | Abramson, Ruth | Betancur, Catalina | Bourgeron, Thomas | Gillberg, Christopher | Leboyer, Marion | Buxbaum, Joseph | Davis, Kenneth | Hollander, Eric | Silverman, Jeremy | Hallmayer, Joachim | Lotspeich, Linda | Sutcliffe, James | Haines, Jonathan | Folstein, Susan | Piven, Joseph | Wassink, Thomas | Sheffield, Val | Geschwind, Daniel | Bucan, Maja | Brown, Ted | Cantor, Rita | Constantino, John | Gilliam, Conrad | Herbert, Martha | Lajonchere, Clara | Ledbetter, David | Lese-Martin, Christa | Miller, Janet | Nelson, Stan | Samango-Sprouse, Carol | Spence, Sarah | State, Matthew | Tanzi, Rudolph | Coon, Hilary | Dawson, Geraldine | Devlin, Bernie | Estes, Annette | Flodman, Pamela | Klei, Lambertus | Mcmahon, William | Minshew, Nancy | Munson, Jeff | Korvatska, Elena | Rodier, Patricia | Schellenberg, Gerard | Smith, Moyra | Spence, Anne | Stodgell, Chris | Tepper, Ping Guo | Wijsman, Ellen | Yu, Chang-En | Rogé, Bernadette | Mantoulan, Carine | Wittemeyer, Kerstin | Poustka, Annemarie | Felder, Bärbel | Klauck, Sabine | Schuster, Claudia | Poustka, Fritz | Bölte, Sven | Feineis-Matthews, Sabine | Herbrecht, Evelyn | Schmötzer, Gabi | Tsiantis, John | Papanikolaou, Katerina | Maestrini, Elena | Bacchelli, Elena | Blasi, Francesca | Carone, Simona | Toma, Claudio | Van Engeland, Herman | De Jonge, Maretha | Kemner, Chantal | Koop, Frederieke | Langemeijer, Marjolein | Hijmans, Channa | Staal, Wouter | Baird, Gillian | Bolton, Patrick | Rutter, Michael | Weisblatt, Emma | Green, Jonathan | Aldred, Catherine | Wilkinson, Julie-Anne | Pickles, Andrew | Le Couteur, Ann | Berney, Tom | Mcconachie, Helen | Bailey, Anthony | Francis, Kostas | Honeyman, Gemma | Hutchinson, Aislinn | Parr, Jeremy | Wallace, Simon | Monaco, Anthony | Barnby, Gabrielle | Kobayashi, Kazuhiro | Lamb, Janine | Sousa, Ines | Sykes, Nuala | Cook, Edwin | Guter, Stephen | Leventhal, Bennett | Salt, Jeff | Lord, Catherine | Corsello, Christina | Hus, Vanessa | Weeks, Daniel | Volkmar, Fred | Tauber, Maïté | Fombonne, Eric | Shih, Andy | Meyer, Kacie
Nature Genetics  2007;39(3):319-328.
Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD.
PMCID: PMC4867008  PMID: 17322880
Chromosome Aberrations; Lod Score; Genetic Testing; Genetic Variation; Humans; Male; Risk Factors; Autistic Disorder; Chromosome Mapping; Family; Female; Genetic Linkage; Genetic Predisposition to Disease

Results 1-3 (3)