Newly discovered gene variants lead to autism and mental retardation

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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.

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 genetic mechanisms 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 nerve impulses be correctly transmitted.

The researchers analyzed the genetic material 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 autism, which can now be explained by a common genetic cause.

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 , 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

Provided by University Hospital Heidelberg