Newly discovered gene variants lead to autism and mental retardation

May 25, 2010

Researchers working with Professor Gudrun Rappold, Director of the Department of Molecular Human Genetics at Heidelberg University Hospital, have discovered previously unknown mutations in autistic and mentally impaired patients in what is known as the SHANK2 gene, a gene that is partially responsible for linking nerve cells. However, a single gene mutation is not always enough to trigger the illness.

In some cases, a certain threshold of mutation must be exceeded. The researchers conclude from their results that a correct inner structure of the nerve cell synapses is necessary to enable the normal development of language, social competence, and cognitive capacity. Essential for the success of the project were the studies by the Heidelberg research team with the doctoral student Simone Berkel and collaboration with a Canadian research team headed by Steve Scherer. The study has already been published online in the leading scientific journal Nature Genetics.

Autism is a congenital perception and information-processing disorder of the brain that is often associated with low intelligence, but also with above-average intelligence. The disease is characterized by limited social communication and stereotypical or ritualized behavior. Men are affected much more frequently than women. Autism and mental retardation can occur together but also independently of one another and are determined to a great extent by hereditary factors. Some of the responsible genes have already been identified but the precise have not yet been explained.

Genetic makeup of hundreds of patients analyzed

Professor Rappold and her team focused their studies on the SHANK2 gene, which encodes a structural protein at the nerve cell synapses. It is responsible for the mesh structure of the basic substance in the postsynapse. Only when the postsynapse is properly structured can be correctly transmitted. The researchers analyzed the of a total of 396 patients with autism and 184 patients with mental retardation. They found different mutations in their SHANK2 genes in the area of individual base pairs, but also variants in the number of gene copies. The mutations led to varying degrees of symptoms. None of the observed gene variants occurred in healthy control persons. "Apparently an intact postsynaptic structure is especially important for the development of cognitive functions, language, and social competence," explained Professor Rappold.

Identical mutations as the cause of different diseases

Some of the genetic mutations identified were new occurrences of mutations that were not inherited from the parents, but some of the mutations were also found in one parent. Since there are also healthy carriers of gene variants, we must assume that a certain threshold of gene mutations must be exceeded for the disease to appear. "Moreover, the same mutation can be present in an autistic patient with normal intelligence and in a mentally impaired patient," said Professor Rappold. There is some overlap in the clinical symptoms of mental retardation and , which can now be explained by a common genetic cause.

Explore further: First genetic link discovered to difficult-to-diagnose breast cancer sub-type

More information: Mutations detected in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. S Berkel, CR Marshall, B Weiss, J Howe, R Roeth, U Moog, V Endris, W Roberts, P Szatmari, D Pinto, M Bonin, A Riess, H Engels, R Sprengel, SW Scherer, GA Rappold, Nature Genetics, 2010 in press (tracking number NG-LE27550R1; manuscript ID 589) Doi:10.1038/ng.589

add to favorites email to friend print save as pdf

Related Stories

Multiple genes implicated in autism

Feb 09, 2009

(PhysOrg.com) -- By pinpointing two genes that cause autism-like symptoms in mice, researchers at MIT’s Picower Institute for Learning and Memory have shown for the first time that multiple, interacting genetic risk factors ...

Tiny, spontaneous gene mutations may boost autism risk

Mar 15, 2007

Tiny gene mutations, each individually rare, pose more risk for autism than had been previously thought, suggests a study funded in part by the National Institute of Mental Health, a component of the National Institutes of ...

Study adds to evidence that autism has genetic basis

May 02, 2010

Although there is no known cause of autism, studies have shown that mutations in several genes are associated with the developmental brain disorder. New research has uncovered two additional genes that may be involved with ...

Severe mental retardation gene mutation identified

Mar 20, 2007

Researchers have identified a novel gene mutation that causes X-linked mental retardation for which there was no previously known molecular diagnosis, according to an article to be published electronically on Tuesday, March ...

Recommended for you

Refining the language for chromosomes

22 hours ago

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in ...

Down's chromosome cause genome-wide disruption

Apr 16, 2014

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

User comments : 0

More news stories

Vietnam battles fatal measles outbreak

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

Continents may be a key feature of Super-Earths

Huge Earth-like planets that have both continents and oceans may be better at harboring extraterrestrial life than those that are water-only worlds. A new study gives hope for the possibility that many super-Earth ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Under some LED bulbs whites aren't 'whiter than white'

For years, companies have been adding whiteners to laundry detergent, paints, plastics, paper and fabrics to make whites look "whiter than white," but now, with a switch away from incandescent and fluorescent lighting, different ...