pubmed: autism and genetics

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Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion.

April 5, 2014 - 3:51pm

Clinical, cytogenetic, and molecular characterization of six patients with ring chromosomes 22, including one with concomitant 22q11.2 deletion.

Am J Med Genet A. 2014 Apr 3;

Authors: Guilherme RS, Soares KC, Simioni M, Vieira TP, Gil-da-Silva-Lopes VL, Kim CA, Brunoni D, Spinner NB, Conlin LK, Christofolini DM, Kulikowski LD, Steiner CE, Melaragno MI

Abstract
We report here on six patients with a ring chromosome 22 and the range of cytogenetic and phenotypic features presented by them. Genomic analysis was carried out using classical and molecular cytogenetics, MLPA (Multiplex Ligation-dependent Probe Amplification) and genome-wide SNP-array analysis. The ring was found in all patients, but Patient 6 displayed constitutional mosaicism with a normal cell line. Five patients had deletions in the ring chromosome 22, and in four of them the breakpoints-unique for each patient-could be identified by genome-wide SNP-array analysis. One patient presented with a 22q11.2 deletion concomitant with the deletion caused by the ring formation. Common phenotypic features included autism, speech delay and seizures, as previously reported for individuals with r(22) and/or 22q13.3 deletions. Investigation of the genes within the deletions revealed multiple genes related to development of the central nervous system, psychomotor delay, severe language impairment, hypotonia, and autistic symptoms. There was no clear correlation between the severity of clinical features and the size of the deleted segment. This study underscores the variability in ring structure and clinical presentation of the r(22) and adds information to the limited literature on this rare disorder. © 2014 Wiley Periodicals, Inc.

PMID: 24700634 [PubMed - as supplied by publisher]

The relationship of neuroimaging findings and neuropsychiatric comorbidities in children with tuberous sclerosis complex.

April 5, 2014 - 3:51pm

The relationship of neuroimaging findings and neuropsychiatric comorbidities in children with tuberous sclerosis complex.

J Formos Med Assoc. 2014 Mar 31;

Authors: Huang CH, Peng SS, Weng WC, Su YN, Lee WT, National Taiwan University Hospital Tuberous Sclerosis Complex (NTUH TSC) Study Group

Abstract
BACKGROUND/PURPOSE: To clarify the relationship between neuroimaging findings, neuropsychiatric comorbidities, and epilepsy in patients with tuberous sclerosis complex (TSC) in Taiwan.
METHODS: Medical records from 32 patients with TSC were retrospectively reviewed, including mutational analysis, neuroimaging findings, electroencephalogram findings, and neuropsychiatric comorbidities.
RESULTS: Of these patients, six (18.75%) were diagnosed to have autism spectrum disorders (ASD), and 10 (31.25%) were diagnosed to have attention-deficit-hyperactivity disorder. In the latter patients, there were no differences in the regional distribution of tuber burden. In addition to a high prevalence of cystic-like tubers, tubers in insular and temporal areas were associated with ASD. Nonsense mutations in the TSC2 gene group had a correlation with autistic behavior. In 26 (81.25%) patients with a history of epilepsy, infantile spasms and partial seizures were the predominant type of epilepsy. Most of them developed seizures prior to age 1 year.
CONCLUSION: ASD is a common comorbidity in TSC. Cortical tubers in the temporal lobe and insular area were associated with ASD. The presence of cystic-like tubers on magnetic resonance imaging may also offer a structural marker for ASD in TSC.

PMID: 24698169 [PubMed - as supplied by publisher]

De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability and, autistic behaviors and epilepsy.

April 5, 2014 - 3:51pm

De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability and, autistic behaviors and epilepsy.

Clin Genet. 2014 Apr 3;

Authors: Nakajima J, Okamoto N, Tohyama J, Kato M, Arai H, Funahashi O, Tsurusaki Y, Nakashima M, Hisashi K, Saitsu H, Matsumoto N, Miyake N

Abstract
Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G>A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G>C, p.Asp252His and c.364G>A, p.Glu122Lys) in EEF1A2 found by whole exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

PMID: 24697219 [PubMed - as supplied by publisher]

Association of the catechol-o-methyltransferase gene polymorphisms with Korean autism spectrum disorders.

April 5, 2014 - 3:51pm
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Association of the catechol-o-methyltransferase gene polymorphisms with Korean autism spectrum disorders.

J Korean Med Sci. 2013 Sep;28(9):1403-6

Authors: Yoo HJ, Cho IH, Park M, Yang SY, Kim SA

Abstract
This study evaluated the family-based genetic association between autism spectrum disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios (dominant model Z = 2.598, P = 0.009, P FDR = 0.045). We found a statistically significant allele transmission or association in terms of the rs6269 SNP in the ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269 demonstrated significant evidence of an association with ASDs (additive model rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P FDR = 0.040). Thus, an association may exist between the variants of the COMT gene and the occurrence of ASDs in Koreans.

PMID: 24015051 [PubMed - indexed for MEDLINE]

CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.

April 5, 2014 - 3:51pm
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CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.

J Psychiatr Res. 2013 Oct;47(10):1349-56

Authors: Clemm von Hohenberg C, Wigand MC, Kubicki M, Leicht G, Giegling I, Karch S, Hartmann AM, Konte B, Friedl M, Ballinger T, Eckbo R, Bouix S, Jäger L, Shenton ME, Rujescu D, Mulert C

Abstract
CNTNAP2 is a gene on chromosome 7 that has shown associations with autism and schizophrenia, and there is evidence that it plays an important role for neuronal synchronization and brain connectivity. In this study, we assessed the relationship between Diffusion Tensor Imaging (DTI), a putative marker of anatomical brain connectivity, and multiple single nucleotide polymorphisms (SNPs) spread out over this large gene. 81 healthy controls and 44 patients with schizophrenia (all Caucasian) underwent DTI and genotyping of 31 SNPs within CNTNAP2. We employed Tract-based Spatial Statistics (TBSS) for inter-subject brain registration and computed average diffusivity values for six major white matter tracts. Analyses of Covariance (ANCOVAs) were computed to test for possible associations with genotypes. The strongest association, which survived rigorous Bonferroni correction, was between rs2710126 genotype and Fractional Anisotropy (FA) in the uncinate fasciculus (p = .00003). This anatomical location is particularly interesting given the enriched fronto-temporal expression of CNTNAP2 in the developing brain. For this SNP, no phenotype association has been reported before. There were several further genotype-DTI associations that were nominally significant but did not survive Bonferroni correction, including an association between axial diffusivity in the dorsal cingulum bundle and a region in intron 13 (represented by rs2710102, rs759178, rs2538991), which has previously been reported to be associated with anterior-posterior functional connectivity. We present new evidence about the effects of CNTNAP2 on brain connectivity, whose disruption has been hypothesized to be central to schizophrenia pathophysiology.

PMID: 23871450 [PubMed - indexed for MEDLINE]

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