Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly / Kim L. MCBRIDE in Autism Research, 3-3 (June 2010)  

Public ISBD [article]  inAutism Research > 3-3 (June 2010) . - p.137-141 Titre : Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly Type de document : Texte imprimé et/ou numérique Auteurs : Kim L. MCBRIDE, Auteur ; Elizabeth A. VARGA, Auteur ; Matthew T. PASTORE, Auteur ; Thomas W. PRIOR, Auteur ; Kandamurugu MANICKAM, Auteur ; Joan F. ATKIN, Auteur ; Gail E. HERMAN, Auteur Année de publication : 2010 Article en page(s) : p.137-141 Langues : Anglais (eng) Mots-clés : genetic Cowden-syndrome molecular-genetics PTEN cancer autism developmental-delay Index. décimale : PER Périodiques Résumé : There is a strong genetic component to autism spectrum disorders (ASD), but due to significant genetic heterogeneity, individual genetic abnormalities contribute a small percentage to the overall total. Previous studies have demonstrated PTEN mutations in a sizable proportion of individuals with ASD or mental retardation/developmental delays (MR/DD) and macrocephaly that do not have features of Cowden or Bannayan-Riley-Ruvalcaba syndrome. This study was performed to confirm our previous results. We reviewed the charts of individuals who had PTEN clinical sequencing performed at our institution from January 2008 to July 2009. There were 93 subjects tested from our institution during that period. PTEN mutations were found in 2/39 (5.1%) ASD patients and 2/51 (3.9%) MR/DD patients. Three additional patients without mutations had no diagnostic information. Multiple relatives of individuals with a PTEN mutation had macrocephaly, MR, or early onset cancer (breast, renal, and prostate). Of those relatives tested, all had the familial PTEN mutation. None of the affected relatives had previously been diagnosed with Cowden or Bannayan-Riley-Ruvalcaba syndrome. We noted in our previous study several adult relatives without any findings who carried a mutation. Combined with data from our previous cohort, we have found PTEN mutations in 7/99 (7.1%) of individuals with ASD and 8/100 (8.0%) of individuals with MR/DD, all of whom had macrocephaly. We recommend testing for mutations in PTEN for individuals with ASD or MR/DD and macrocephaly. If mutations are found, other family members should be offered testing and the adults offered cancer screening if they have a PTEN mutation. En ligne : http://dx.doi.org/10.1002/aur.132 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=107 [article] Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly [Texte imprimé et/ou numérique] / Kim L. MCBRIDE, Auteur ; Elizabeth A. VARGA, Auteur ; Matthew T. PASTORE, Auteur ; Thomas W. PRIOR, Auteur ; Kandamurugu MANICKAM, Auteur ; Joan F. ATKIN, Auteur ; Gail E. HERMAN, Auteur . - 2010 . - p.137-141. Langues : Anglais (eng) in Autism Research > 3-3 (June 2010) . - p.137-141 Mots-clés : genetic Cowden-syndrome molecular-genetics PTEN cancer autism developmental-delay Index. décimale : PER Périodiques Résumé : There is a strong genetic component to autism spectrum disorders (ASD), but due to significant genetic heterogeneity, individual genetic abnormalities contribute a small percentage to the overall total. Previous studies have demonstrated PTEN mutations in a sizable proportion of individuals with ASD or mental retardation/developmental delays (MR/DD) and macrocephaly that do not have features of Cowden or Bannayan-Riley-Ruvalcaba syndrome. This study was performed to confirm our previous results. We reviewed the charts of individuals who had PTEN clinical sequencing performed at our institution from January 2008 to July 2009. There were 93 subjects tested from our institution during that period. PTEN mutations were found in 2/39 (5.1%) ASD patients and 2/51 (3.9%) MR/DD patients. Three additional patients without mutations had no diagnostic information. Multiple relatives of individuals with a PTEN mutation had macrocephaly, MR, or early onset cancer (breast, renal, and prostate). Of those relatives tested, all had the familial PTEN mutation. None of the affected relatives had previously been diagnosed with Cowden or Bannayan-Riley-Ruvalcaba syndrome. We noted in our previous study several adult relatives without any findings who carried a mutation. Combined with data from our previous cohort, we have found PTEN mutations in 7/99 (7.1%) of individuals with ASD and 8/100 (8.0%) of individuals with MR/DD, all of whom had macrocephaly. We recommend testing for mutations in PTEN for individuals with ASD or MR/DD and macrocephaly. If mutations are found, other family members should be offered testing and the adults offered cancer screening if they have a PTEN mutation. En ligne : http://dx.doi.org/10.1002/aur.132 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=107

Contactin 4 as an autism susceptibility locus / Catherine E. COTTRELL in Autism Research, 4-3 (June 2011)  

Public ISBD [article]  inAutism Research > 4-3 (June 2011) . - p.189-199 Titre : Contactin 4 as an autism susceptibility locus Type de document : Texte imprimé et/ou numérique Auteurs : Catherine E. COTTRELL, Auteur ; Natalie BIR, Auteur ; Elizabeth A. VARGA, Auteur ; Carlos E. ALVAREZ, Auteur ; Samuel BOUYAIN, Auteur ; Randall ZERNZACH, Auteur ; Devon L. THRUSH, Auteur ; Johnna EVANS, Auteur ; Michael TRIMARCHI, Auteur ; Eric BUTTER, Auteur ; David CUNNINGHAM, Auteur ; Julie M. GASTIER-FOSTER, Auteur ; Kim L. MCBRIDE, Auteur ; Gail E. HERMAN, Auteur Année de publication : 2011 Article en page(s) : p.189-199 Langues : Anglais (eng) Mots-clés : contactin 4  autism  autism spectrum disorder  3p26 deletion  contactins  susceptibility locus Index. décimale : PER Périodiques Résumé : Structural and sequence variation have been described in several members of the contactin (CNTN) and contactin-associated protein (CNTNAP) gene families in association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ∼535 kb deletion at 3p26.3 encompassing the 5′ end of the contactin 4 gene (CNTN4) in a patient with autism. Based on this finding and previous reports implicating genomic rearrangements of CNTN4 in autism spectrum disorders (ASDs) and 3p− microdeletion syndrome, we undertook sequencing of the coding regions of the gene in a local ASD cohort in comparison with a set of controls. Unique missense variants were identified in 4 of 75 unrelated individuals with ASD, as well as in 1 of 107 controls. All of the amino acid substitutions were nonsynonomous, occurred at evolutionarily conserved positions, and were, thus, felt likely to be deleterious. However, these data did not reach statistical significance, nor did the variants segregate with disease within all of the ASD families. Finally, there was no detectable difference in binding of two of the variants to the interacting protein PTPRG in vitro. Thus, additional larger studies will be necessary to determine whether CNTN4 functions as an autism susceptibility locus in combination with other genetic and/or environmental factors. En ligne : http://dx.doi.org/10.1002/aur.184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127 [article] Contactin 4 as an autism susceptibility locus [Texte imprimé et/ou numérique] / Catherine E. COTTRELL, Auteur ; Natalie BIR, Auteur ; Elizabeth A. VARGA, Auteur ; Carlos E. ALVAREZ, Auteur ; Samuel BOUYAIN, Auteur ; Randall ZERNZACH, Auteur ; Devon L. THRUSH, Auteur ; Johnna EVANS, Auteur ; Michael TRIMARCHI, Auteur ; Eric BUTTER, Auteur ; David CUNNINGHAM, Auteur ; Julie M. GASTIER-FOSTER, Auteur ; Kim L. MCBRIDE, Auteur ; Gail E. HERMAN, Auteur . - 2011 . - p.189-199. Langues : Anglais (eng) in Autism Research > 4-3 (June 2011) . - p.189-199 Mots-clés : contactin 4  autism  autism spectrum disorder  3p26 deletion  contactins  susceptibility locus Index. décimale : PER Périodiques Résumé : Structural and sequence variation have been described in several members of the contactin (CNTN) and contactin-associated protein (CNTNAP) gene families in association with neurodevelopmental disorders, including autism. Using array comparative genome hybridization (CGH), we identified a maternally inherited ∼535 kb deletion at 3p26.3 encompassing the 5′ end of the contactin 4 gene (CNTN4) in a patient with autism. Based on this finding and previous reports implicating genomic rearrangements of CNTN4 in autism spectrum disorders (ASDs) and 3p− microdeletion syndrome, we undertook sequencing of the coding regions of the gene in a local ASD cohort in comparison with a set of controls. Unique missense variants were identified in 4 of 75 unrelated individuals with ASD, as well as in 1 of 107 controls. All of the amino acid substitutions were nonsynonomous, occurred at evolutionarily conserved positions, and were, thus, felt likely to be deleterious. However, these data did not reach statistical significance, nor did the variants segregate with disease within all of the ASD families. Finally, there was no detectable difference in binding of two of the variants to the interacting protein PTPRG in vitro. Thus, additional larger studies will be necessary to determine whether CNTN4 functions as an autism susceptibility locus in combination with other genetic and/or environmental factors. En ligne : http://dx.doi.org/10.1002/aur.184 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127

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