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Sex-Specific Placental Responses in Fetal Development.

August 5, 2015 - 7:42am

Sex-Specific Placental Responses in Fetal Development.

Endocrinology. 2015 Aug 4;:en20151227

Authors: Rosenfeld CS

Abstract
The placenta is an ephemeral but critical organ for the survival of all eutherian mammals and marsupials. It is the primary messenger system between the mother and fetus, where communicational signals, nutrients, waste, gases, and extrinsic factors are exchanged. Although the placenta may buffer the fetus from various environmental insults, placental dysfunction might also contribute to detrimental developmental origins of adult health and disease effects. The placenta of one sex over the other might possess greater ability to respond and buffer against environmental insults. Given the potential role of the placenta in effecting the lifetime health of the offspring, it is not surprising that there has been a resurging interest in this organ, including the Human Placental Project launched by the National Institutes of Child Health and Human Development. In this review, we will compare embryological development of the laboratory mouse and human chorioallantoic placentae. Next, evidence that various species, including humans, exhibit normal sex-dependent structural and functional placental differences will be examined followed by how in utero environmental changes (nutritional state, stress, and exposure to environmental chemicals) might interact with fetal sex to affect this organ. Recent data also suggest that paternal state impacts placental function in a sex-dependent manner. The research to date linking placental maladaptive responses and later developmental origins of adult health and disease effects will be explored. Finally, we will focus on how sex chromosomes and epimutations may contribute to sex-dependent differences in placental function, the unanswered questions, and future directions that warrant further consideration.

PMID: 26241064 [PubMed - as supplied by publisher]

[Molecular basis of Rett syndrome: A current look].

August 5, 2015 - 7:42am

[Molecular basis of Rett syndrome: A current look].

Rev Chil Pediatr. 2015 Jul 31;

Authors: Pantaleón F G, Juvier R T

Abstract
Rett syndrome (RS) is a neurodevelopmental disorder that exclusively affects girls, and occurs along with autism. It is very uncommon, and has five distinct forms, one classic and the others atypical, which generally compromise manual skills, language, and mobility, and widely associated with the appearance of stereotypy and early epilepsy. With the aim of updating the information about RS, a search was performed in the computer data bases of PubMed, Hinari, SCIELO and Medline, as well as consulting other web sites including OMIM, ORPHANET, GeneMap, Genetests, Proteins and Gene, using the descriptors "Síndrome de Rett", "genes y Síndrome de Rett", "Rett Syndrome gene", "Rett Syndrome", "Rett Syndrome gene therapy", and "Rett Syndrome review". Of the 1,348 articles found, 42 articles were selected, which reported 3 genes causing the syndrome: MECP2, CDKL5 and FOXG. The MECP2 gene is mutated in 80% of patients with classic RS, as well as in 40% of those affected by any of its atypical forms. RS with early epilepsy and the congenital variant are mainly due to variations in the CDKL5 and FOXG1 genes, respectively.
CONCLUSIONS: The diagnosis of RS is based on clinical criteria. However, the advances in molecular biology and genetics have opened a wide range of possibilities for diagnosing the different clinical forms that could not be classified before. Molecular analysis can help confirm the clinical criteria and provided information as regards the prognosis of the patient.

PMID: 26239053 [PubMed - as supplied by publisher]

1q21.1 microduplication in a patient with mental impairment and congenital heart defect.

August 5, 2015 - 7:42am

1q21.1 microduplication in a patient with mental impairment and congenital heart defect.

Mol Med Rep. 2015 Jul 31;

Authors: Sun G, Tan Z, Fan L, Wang J, Yang Y, Zhang W

Abstract
1q21.1 duplication is a rare copy number variant with multiple congenital malformations, including developmental delay, autism spectrum disorder, dysmorphic features and congenital heart anomalies. The present study described a Chinese female patient (age, four years and eight months) with multiple malformations, including congenital heart defect, mental impairment and developmental delay. The parents and the monozygotic twin sister of the patient, however, were physically and psychologically normal. High‑resolution genome‑wide single nucleotide polymorphism array revealed a 1.6‑Mb duplication in chromosome region 1q21.1. This chromosome region contained HFE2, a critical gene involved in hereditary hemochromatosis. However, the parents and monozygotic twin sister of the patient did not carry this genomic lesion. To the best of our knowledge, the present study was the first to report on a 1q21.1 duplication patient in mainland China.

PMID: 26238956 [PubMed - as supplied by publisher]

Genetic factors are "substantial" in aetiology of autism, study of UK twins finds.

August 5, 2015 - 7:42am
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Genetic factors are "substantial" in aetiology of autism, study of UK twins finds.

BMJ. 2015;350:h1212

Authors: Wise J

PMID: 25744550 [PubMed - indexed for MEDLINE]

Dysmyelination with preservation of transverse bands in a long-lived allele of the quaking mouse.

August 5, 2015 - 7:42am
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Dysmyelination with preservation of transverse bands in a long-lived allele of the quaking mouse.

J Comp Neurol. 2015 Feb 1;523(2):197-208

Authors: Chaverneff F, Mierzwa A, Weinstock M, Ketcham M, Lang EJ, Rosenbluth J

Abstract
The new mutant mouse shaking (shk) differs from other "myelin mutants" in having a more stable neurological impairment and a much longer lifespan. We have shown that transverse bands (TBs), the component of the paranodal junction (PNJ) that attaches the myelin sheath to the axon, are present in the shk central nervous system (CNS), in contrast to more severely affected mutants, in which TBs are absent or rare. We have proposed that TBs are the major determinant underlying shk neurological stability and longevity. Here we report that TBs are abundant not only in the shk CNS but also in its peripheral nervous system (PNS), which, as in other "myelin mutants", is not as severely dysmyelinated as the CNS but does display structural abnormalities likely to affect impulse propagation. In particular, myelin sheaths are thinner than normal, and some axonal segments lack myelin sheaths entirely. In addition, we establish that the shk mutation, previously localized to chromosome 17, is a quaking (qk) allele consisting of a 105-nucleotide insertion in the qk regulatory region that decreases qk transcription but does not extend to the Parkin and Parkin coregulated genes, which are affected in the qk allele. We conclude that: 1) dysmyelination is less severe in the shk PNS than in the CNS, but TBs, which are present in both locations, stabilize the PNJs and prevent the progressive neurological deficits seen in mutants lacking TBs; and 2) the insertional mutation in shk mice is sufficient to produce the characteristic neurological phenotype without involvement of the Parkin and Parkin coregulated genes.

PMID: 25185516 [PubMed - indexed for MEDLINE]

A recurrent deletion on chromosome 2q13 is associated with developmental delay and mild facial dysmorphisms.

August 4, 2015 - 6:36am
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A recurrent deletion on chromosome 2q13 is associated with developmental delay and mild facial dysmorphisms.

Mol Cytogenet. 2015;8:57

Authors: Hladilkova E, Barøy T, Fannemel M, Vallova V, Misceo D, Bryn V, Slamova I, Prasilova S, Kuglik P, Frengen E

Abstract
We report two unrelated patients with overlapping chromosome 2q13 deletions (patient 1 in chr2:111415137-113194067 bp and patient 2 in chr2:110980342-113007823 bp, hg 19). Patient 1 presents with developmental delay, microcephaly and mild dysmorphic facial features, and patient 2 with autism spectrum disorder, borderline cognitive abilities, deficits in attention and executive functions and mild dysmorphic facial features. The mother and maternal grandmother of patient 1 were healthy carriers of the deletion. Previously, 2q13 deletions were reported in 27 patients, and the interpretation of its clinical significance varied. Our findings support that the 2q13 deletion is associated with a developmental delay syndrome manifesting with variable expressivity and reduced penetrance which poses a challenge for genetic counselling as well as the clinical recognition of 2q13 deletion patients.

PMID: 26236398 [PubMed]

Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample.

August 4, 2015 - 6:36am
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Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample.

JAMA Psychiatry. 2015 May;72(5):415-23

Authors: Colvert E, Tick B, McEwen F, Stewart C, Curran SR, Woodhouse E, Gillan N, Hallett V, Lietz S, Garnett T, Ronald A, Plomin R, Rijsdijk F, Happé F, Bolton P

Abstract
IMPORTANCE: Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.
OBJECTIVES: To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.
DESIGN, SETTING, AND PARTICIPANTS: We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs).
MAIN OUTCOMES AND MEASURES: Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis.
RESULTS: On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]).
CONCLUSIONS AND RELEVANCE: The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.

PMID: 25738232 [PubMed - indexed for MEDLINE]

Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012.

August 1, 2015 - 6:39am
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Is it possible to diagnose Rett syndrome before classical symptoms become obvious? Review of 24 Danish cases born between 2003 and 2012.

Eur J Paediatr Neurol. 2015 Jul 21;

Authors: Bisgaard AM, Schönewolf-Greulich B, Ravn K, Rønde G

Abstract
BACKGROUND/PURPOSE: Rett syndrome (RTT) is a neurodevelopmental disorder that affects mainly females; it results in multiple disabilities and carries a risk of medical comorbidities. Early diagnosis is important to help establish the best treatment opportunities and preventive care in order to slow down the progression of symptoms. We wanted to test our hypothesis that it is possible to diagnose RTT before the classical symptoms become obvious.
METHODS: We analysed development and symptoms before and at the time of the RTT diagnosis, as well as the symptoms that triggered MECP2 mutation analysis, in a cohort of girls with RTT born in Denmark between 2003 and 2012.
RESULTS: Twenty-four girls were included, and 87.5% of these girls were diagnosed when the classical RTT symptoms were recognized. However, parents were concerned about their daughters between 3 and 58 months prior to the RTT diagnosis, and they felt that the professionals did not share their concern in the beginning. When reviewing medical files and questionnaires, we noted that the majority of girls did have combinations of concerning symptoms such as developmental delay and a collection of subtle signs such as autistic traits, placidity, floppiness with suspicion of muscular or mitochondrial diseases, hair pulling, teeth grinding, development of incontinence and problems with initiating movements.
CONCLUSION: We conclude that many individuals with MECP2 mutation exhibit characteristics that should raise suspicion for RTT, prior to evolution of the core clinical criteria. As RTT is a rare disease, it is of importance to constantly educate clinicians for heightened awareness of RTT.

PMID: 26228846 [PubMed - as supplied by publisher]

Recurrent deletions and duplications of chromosome 2q11.2 and 2q13 are associated with variable outcomes.

August 1, 2015 - 6:39am
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Recurrent deletions and duplications of chromosome 2q11.2 and 2q13 are associated with variable outcomes.

Am J Med Genet A. 2015 Jul 31;

Authors: Riley KN, Catalano LM, Bernat JA, Adams SD, Martin DM, Lalani SR, Patel A, Burnside RD, Innis JW, Rudd MK

Abstract
Copy number variation (CNV) in the long arm of chromosome 2 has been implicated in developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), congenital anomalies, and psychiatric disorders. Here we describe 14 new subjects with recurrent deletions and duplications of chromosome 2q11.2, 2q13, and 2q11.2-2q13. Though diverse phenotypes are associated with these CNVs, some common features have emerged. Subjects with 2q11.2 deletions often exhibit DD, speech delay, and attention deficit hyperactivity disorder (ADHD), whereas those with 2q11.2 duplications have DD, gastroesophageal reflux, and short stature. Congenital heart defects (CHDs), hypotonia, dysmorphic features, and abnormal head size are common in those with 2q13 deletions. In the 2q13 duplication cohort, we report dysmorphic features, DD, and abnormal head size. Two individuals with large duplications spanning 2q11.2-2q13 have dysmorphic features, hypotonia, and DD. This compilation of clinical features associated with 2q CNVs provides information that will be useful for healthcare providers and for families of affected children. However, the reduced penetrance and variable expressivity associated with these recurrent CNVs makes genetic counseling and prediction of outcomes challenging. © 2015 Wiley Periodicals, Inc.

PMID: 26227573 [PubMed - as supplied by publisher]

Tuberous sclerosis complex.

August 1, 2015 - 6:39am
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Tuberous sclerosis complex.

Pediatr Clin North Am. 2015 Jun;62(3):633-48

Authors: DiMario FJ, Sahin M, Ebrahimi-Fakhari D

Abstract
Tuberous sclerosis complex is an autosomal-dominant, neurocutaneous, multisystem disorder characterized by cellular hyperplasia and tissue dysplasia. The genetic cause is mutations in the TSC1 gene, found on chromosome 9q34, and TSC2 gene, found on chromosome 16p13. The clinical phenotypes resulting from mutations in either of the 2 genes are variable in each individual. Herein, advances in the understanding of molecular mechanisms in tuberous sclerosis complex are reviewed, and current guidelines for diagnosis, treatment, follow-up, and management are summarized.

PMID: 26022167 [PubMed - indexed for MEDLINE]

Autism is (also) a movement disorder.

August 1, 2015 - 6:39am
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Autism is (also) a movement disorder.

Mov Disord. 2015 Mar;30(3):341

Authors: Jaber M

PMID: 25702637 [PubMed - indexed for MEDLINE]

La FAM fatale: USP9X in development and disease.

August 1, 2015 - 6:39am
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La FAM fatale: USP9X in development and disease.

Cell Mol Life Sci. 2015 Jun;72(11):2075-89

Authors: Murtaza M, Jolly LA, Gecz J, Wood SA

Abstract
Deubiquitylating enzymes (DUBs), act downstream of ubiquitylation. As such, these post-post-translational modifiers function as the final arbitrators of a protein substrate's ubiquitylation status, thus regulating its fate. In most instances, DUBs moderate the absolute level of a substrate, its locality or activity, rather than being an "all-or-none" phenomenon. Yet, disruption of this quantitative regulation can produce dramatic qualitative differences. The ubiquitin-specific protease 9X (USP9X/FAM) is a substrate-specific DUB, which displays an extraordinarily high level of sequence conservation from Drosophila to mammals. It is primarily the recent revelations of USP9X's pivotal role in human cancers, both as oncogene or tumour suppressor, in developmental disorders including intellectual disability, epilepsy, autism and developmental delay that has led to a subsequent re-examination of its molecular and cellular functions. Results from experimental animal models have implicated USP9X in neurodegeneration, including Parkinson's and Alzheimer's disease, as well as autoimmune diseases. In this review, we describe the current and accumulated knowledge on the molecular, cellular and developmental aspects of USP9X function within the context of the biological consequences during normal development and disease.

PMID: 25672900 [PubMed - indexed for MEDLINE]

Anti-neuronal antibodies in patients with fragile X syndrome: is there a role of autoimmunity in its pathogenesis?

August 1, 2015 - 6:39am
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Anti-neuronal antibodies in patients with fragile X syndrome: is there a role of autoimmunity in its pathogenesis?

Neurodegener Dis. 2015;15(1):45-9

Authors: Lisik MZ, Gutmajster E, Sieroń AL

Abstract
BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and a strong association with autism.
OBJECTIVES: In this study, the frequency of serum anti-neural antibodies was investigated in FXS patients who did and those who did not manifest autism spectrum disorders (ASD) in comparison to typically developing controls.
METHODS: The study involved 23 males (mean age, 19.78 ± 6.56 years) who harboured a full mutation in the FMR1 gene. The control group comprised 19 healthy students (mean age 24.63 ± 1.89 years). Serum anti-neuronal antibodies were analyzed using Western blotting.
RESULTS: Serum anti-neuronal antibodies were present in 10/23 (43.48%) FXS males.
CONCLUSION: Serum anti-neuronal antibodies were found in a subgroup of FXS patients. Autistic symptoms in FXS may, in part, be caused by auto-immune factors. Further studies in larger patient and control groups are necessary to elucidate the aetiopathogenic role of anti-neuronal antibodies in FXS patients.

PMID: 25500855 [PubMed - indexed for MEDLINE]

Recurrent de novo mutations implicate novel genes underlying simplex autism risk.

August 1, 2015 - 6:39am
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Recurrent de novo mutations implicate novel genes underlying simplex autism risk.

Nat Commun. 2014;5:5595

Authors: O'Roak BJ, Stessman HA, Boyle EA, Witherspoon KT, Martin B, Lee C, Vives L, Baker C, Hiatt JB, Nickerson DA, Bernier R, Shendure J, Eichler EE

Abstract
Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.

PMID: 25418537 [PubMed - indexed for MEDLINE]

Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.

August 1, 2015 - 6:39am
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Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.

Nat Commun. 2014;5:5586

Authors: Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, Wan V, Simmons DH, Eissa T, Nakatani J, Cherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang SS, Hansel C

Abstract
A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning--a form of cerebellum-dependent motor learning--is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres--a model for activity-dependent synaptic pruning--is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.

PMID: 25418414 [PubMed - indexed for MEDLINE]

SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: a study from an Indian population.

August 1, 2015 - 6:39am
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SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: a study from an Indian population.

Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jan 2;56:196-206

Authors: Jaiswal P, Guhathakurta S, Singh AS, Verma D, Pandey M, Varghese M, Sinha S, Ghosh S, Mohanakumar KP, Rajamma U

Abstract
Presence of platelet hyperserotonemia and effective amelioration of behavioral dysfunctions by selective serotonin reuptake inhibitors (SSRI) in autism spectrum disorders (ASD) indicate that irregularities in serotonin (5-HT) reuptake and its homeostasis could be the basis of behavioral impairments in ASD patients. SLC6A4, the gene encoding serotonin transporter (SERT) is considered as a potential susceptibility gene for ASD, since it is a quantitative trait locus for blood 5-HT levels. Three functional polymorphisms, 5-HTTLPR, STin2 and 3'UTR-SNP of SLC6A4 are extensively studied for possible association with the disorder, with inconclusive outcome. In the present study, we investigated association of these polymorphisms with platelet 5-HT content and symptoms severity as revealed by childhood autism rating scale in ASD children from an Indian population. Higher 5-HT level observed in ASD was highly significant in children with heterozygous and homozygous genotypes comprising of minor alleles of the markers. Quantitative transmission disequilibrium test demonstrated significant genetic effect of STin2 allele as well as STin2/3'UTR-SNP and 5-HTTLPR/3'UTR-SNP haplotypes on 5-HT levels, but no direct association with overall CARS score and ASD phenotype. Significant genetic effect of the markers on specific behavioral phenotypes was observed for various sub-phenotypes of CARS in quantitative trait analysis. Even though the 5-HT level was not associated with severity of behavioral CARS score, a significant negative relationship was observed for 5-HT levels and level and consistency of intellectual response and general impression in ASD children. Population-based study revealed higher distribution of the haplotype 10/G of STin2/3'UTR-SNP in male controls, suggesting protective effect of this haplotype in male cases. Overall results of the study suggest that SLC6A4 markers have specific genetic effect on individual ASD behavioral attributes, might be through the modulation of 5-HT content.

PMID: 25261775 [PubMed - indexed for MEDLINE]

Autism spectrum disorder: FRAXE mutation, a rare etiology.

July 30, 2015 - 7:04am
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Autism spectrum disorder: FRAXE mutation, a rare etiology.

J Autism Dev Disord. 2015 Mar;45(3):888-92

Authors: Correia F, Café C, Almeida J, Mouga S, Oliveira G

Abstract
Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication, restricted interests and repetitive behaviors. Fragile X E is associated with X-linked non-specific mild intellectual disability (ID) and with behavioral problems. Most of the known genetic causes of ASD are also causes of ID, implying that these two identities share common genetic bases. We present a child with an ASD with a normal range of intelligence quotient, that later evolved to compulsive behavior. FRAXE locus analysis by polymerase chain reaction revealed a complete mutation of the FMR 2 gene. This report stresses the importance of clinicians being aware of the association between a full mutation of FMR2 and ASD associated with compulsive behavior despite normal intellectual level.

PMID: 25035088 [PubMed - indexed for MEDLINE]

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury.

July 29, 2015 - 9:07am

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury.

Sci Total Environ. 2015 Jul 25;536:245-251

Authors: Dickerson AS, Rahbar MH, Han I, Bakian AV, Bilder DA, Harrington RA, Pettygrove S, Durkin M, Kirby RS, Wingate MS, Tian LH, Zahorodny WM, Pearson DA, Moyé LA, Baio J

Abstract
Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

PMID: 26218563 [PubMed - as supplied by publisher]

BDNF Val(66)Met and 5-HTTLPR Genotype are Each Associated with Visual Scanning Patterns of Faces in Young Children.

July 29, 2015 - 9:07am
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BDNF Val(66)Met and 5-HTTLPR Genotype are Each Associated with Visual Scanning Patterns of Faces in Young Children.

Front Behav Neurosci. 2015;9:175

Authors: Christou AI, Wallis Y, Bair H, Crawford H, Frisson S, Zeegers MP, McCleery JP

Abstract
Previous studies have documented both neuroplasticity-related BDNF Val(66)Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relation to BDNF Val(66)Met and 5-HTTLPR genotyping in 49 children aged 4-7 years. Analyses revealed that variations in the visual processing of facial expressions of anger interacted with BDNF Val(66)Met genotype, such that children who carried at least one low neuroplasticity Met allele exhibited a vigilance-avoidance pattern of visual scanning compared to homozygotes for the high neuroplasticity Val allele. In a separate investigation of eye gaze towards the eye versus mouth regions of neutral faces, we observed that short allele 5-HTTLPR carriers exhibited reduced looking at the eye region compared with those with the higher serotonin uptake Long allele. Together, these findings suggest that genetic mechanisms early in life may influence the establishment of patterns of visual scanning of environmental stressors, which in conjunction with other factors such as negative life events, may lead to psychological difficulties and disorders in the later adolescent and adult years.

PMID: 26217202 [PubMed]

Physical biology of human brain development.

July 29, 2015 - 9:07am
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Physical biology of human brain development.

Front Cell Neurosci. 2015;9:257

Authors: Budday S, Steinmann P, Kuhl E

Abstract
Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

PMID: 26217183 [PubMed]

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