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Overview of autism genetics

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An excellent overview of autism genetics:

Identical twin studies put autism’s heritability in a range between 0.36 and 0.957, with concordance for a broader phenotype usually found at the higher end of the range.[1] Autism concordance in siblings and fraternal twins is anywhere between 0 and 23.5%. This is more likely 2–4% for classic autism and 10–20% for a broader spectrum. Assuming a general-population prevalence of 0.1%, the risk of classic autism in siblings is 20- to 40-fold that of the general population. To What Extent Do Genes Cause Autism?

These are the genes that the article runs through:

SERT – rigid compulsive behaviours, social adversity, depression as a result of social adversity, hyperserotonemia.

GABA – GABRA4 through interaction with GABRB1. GABRB3 – savant skills. [Interestingly GABRA1 is associated with Juvenile Myoclonic Epilepsy – the individual I know with JME scores very high-normal on an AQ test.]

Engrailed 2 (EN2) – cerebellar development.

3q25-27 region – autism and asperger’s, function unknown.

7q21-q36 region, REELIN (RELN) – memory formation, neurotransmission, synaptic plasticity.

SLC25A12 – AGC1, mitochondrial aspartate/glutamate carrier.

HOXA1 and HOXB1 – brain stem development. Possibly head circumference. May interact with teratogens like valproic acid. Undermethylation?

PRKCB1 – Protein kinase C beta 1, diverse signalling pathways. Involvement in arachidonic acid cascade?

FOXP2 – Developmental language and speech deficits.

UBE3A – Angelman syndrome, Rett syndrome. Development delay, hand flapping, happy demeanour.

Shank3/ProSAP2, 22q13 and Neuroligins – neuroligins regulate structural organisation of neurotransmitter receptors. SHANK3 – encodes a synaptic scaffolding protein. Interaction between SHANK3 and 22q13 – global development delay, delayed speech, delayed cognitive abilities, high pain tolerance, chewing and mouthing. Neuroligin-3 – poor social skills and increased intelligence.

MET (MET receptor tyrosine kinase) – brain development, regulation of the immune system, repair of GI system. Disrupted neuronal growth in cerebral cortex, smaller cerebellum. MET variants influence cancer metastases – cancer less likely in these autistic children.

Neurexin 1 – CNTNAP2 – communication between nerve cells, regulating chemical transmission, early brain development.

GSTP1 – glutathione s-transferase acting in mother during pregnancy increasing risk of autism in child.

Other candidate loci include the 17q21 region, the 3p24-26 locus, PTEN and 15q11-q13.

Other possibles: SLC6A2 (Social phobia), FMR1 (Fragile-X), 5-HT-1Dbeta (OCD), 7q11.23 (William’s syndrome, language impairment), 4q34-35, 5q35.2-35.3, 17q25 (Tourette syndrome), 2q24.1-31.1 (Intelligence), 6p25.3-22.3 (Verbal IQ), 22q11.2 (Visio-Spatial IQ).

The genes mentioned above aren’t the only genes with suspected involvement in autism – there are methylation genes too:

The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism

And a number of studies linking low functioning MAO with increased severity.

These comments are from the biggest autism twin study mentioned in the article:

High heritability was found for extreme autistic-like traits (0.64-0.92 for various cutoffs) and autistic-like traits as measured on a continuum (0.78-0.81), with no significant shared environmental influences. All three subscales were highly heritable but showed low covariation. In the genetic modeling, distinct genetic influences were identified for the three components. Genetic heterogeneity between the three components of the autism spectrum: a twin study

As you can see there are a huge number of different genes implicated in the etiology of autism. I’ve often thought of the label ‘autism’ as being a bit like a rubbish bin diagnosis into which many different types of people are put because they fit a few basic criteria. In the past those people would have been put into different criteria – for example they would have been defined as ‘retarded’ or ‘psychotic’ or ‘shy’. Some autistics are mentally retarded, some have increased intelligence. Some have savant skills. Some rock and flap and poo smear. Others write computer programs, design jet planes, or teach astrophysics for a living. Some don’t talk at all. Others never stop talking. I identify closely with some of the autistics whose blogs I read (I find myself thinking she’s got exactly the same symptoms/personality as me right the way down to the fear of having to use a telephone). I think other autistics whose blogs I read are just plain weird (I find myself thinking he’s one of those mad/paranoid/illogical/retarded autistics). It takes many different genes to produce many different aspects of the personality.


Written by alienrobotgirl

26 April, 2008 at 5:02 pm

Posted in Autism Genetics

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