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Scientists advance
understanding of the role of a key brain protein in autism |
Results of a genetic linkage analysis of PRKCB1 with autism published
Paris, France, 19 July 2005 …..
Scientists working at IntegraGen SA, the personalized medicines company, have
shown that variations in the gene for protein kinase C beta 1 (PRKCB1), a
protein with an important role in brain function, are strongly associated with
autism. This exciting finding suggests some answers to a number of previous, but
unexplained, observations about autism and provides the potential for a
mechanistic explanation for some of the characteristics of the condition. The
results of the study are published today in the journal Molecular Psychiatry.1
The PRKCB1 gene is
expressed in the granule cells within the cerebellum (a region of the brain)
where the PRKCB1 protein plays a central role in the transmission of signals by
the granule cells to the Purkinje cells. It has previously been reported that
there is a decreased number of both granule and Purkinje cells in the brains of
autistic individuals and the association of PRKCB1 with autism reported in this
study indicates that the cerebellum may play a key role in many of the brain
activities that are impaired in autism. Another intriguing observation is that
studies using animal models have shown that PRKCB1 is involved in auditory
reversal learning. Considered in light of IntegraGen’s results, this suggests
that deficiency of the protein might lead to the impairment of this learning
capacity, as is frequently seen in autism.
“This is the first
time that the protein PRKCB1, and the brain functions it is involved with, have
been associated with autism,” explained Dr Jorg Hager, Chief Scientist at
IntegraGen. “For this reason, we think that this is a significant development in
the field of autism research and we hope it will make an important contribution
to understanding the causes of the condition.”
Autism is a
complex genetic disorder and it is believed that the combined action of a number
of genes may increase a person’s susceptibility to the condition. Genetic
researchers at IntegraGen have been using the Company’s novel GenomeHIP™ method
to identify genes associated with autism. The Company has so far identified 12
regions of the genome linked to autism and, within those, has been able to
specifically identify the region coding for PRKCB1. Work is continuing to
identify further genes associated with autism within those loci identified.
As has been shown
with this study, IntegraGen’s work to identify the genes involved in autism will
contribute towards understanding the mechanisms behind the disease. IntegraGen
plans to use its knowledge of the genetic risk factors to develop a genetic risk
assessment test for the condition, based on the PRKCB1 and additional genes
which it hopes to launch in 2006. The Company envisages that this will be used
to help confirm diagnosis and to help patients and families better understand
the condition and its causes. They hope that it may also prove to be a useful
tool in assessing the risk of the condition developing when a child is still too
young to show clear symptoms, so that informed decisions can be made by
clinicians as to the use of interventional therapies as early and as
appropriately as possible, at a time when they are known to be most effective.
- ENDS -
1.
Philippi A, Roschmann
E, Tores F, Lindenbaum P, Benajou A, Germain-LeClerc L,
et al. Haplotypes in the gene
encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with
autism. Mol Psychiatry, advance online publication, July 19, 2005;
doi:10.1038/sj.mp.4001704.
Notes to editors:
About the study
IntegraGen applied
its GenomeHIP™ method to 116 families from the Autism Genetics Resource Exchange
(AGRE) DNA repository and identified 12 genetic loci (genome regions) linked to
autism, including the PRKCB1 locus. High resolution Single Nucleotide
Polymorphism (SNP) mapping analysis of the region showed that variations within
the PRKCB1 gene are strongly associated with autism. An independent replication
of the association in a second set of 167 families with autism confirmed the
findings.
About IntegraGen
IntegraGen SA uses
its unique genomic analysis expertise to identify genes associated with complex
diseases and to develop diagnostic and predictive genetic tests. The Company
applies its innovative gene mapping technology, GenomeHIP® (Genome Hybrid
Identity Profiling), to rapidly discover genetic loci that are implicated in
complex, multi-factorial diseases. GenomeHIP® is a major advance that overcomes
the limitations of existing marker based familial linkage study methods.
IntegraGen is
applying its discoveries to develop a series of innovative IntegraTests™ and is
poised to become a leader in the rapidly growing field of predictive medicine.
The Company will be a fully integrated provider of genetic tests that can be
used to predict, prevent, diagnose and tailor personalized treatments for
complex diseases. Testing will be provided as a service through Expert Centers,
which will also provide expert analysis and genetic counseling from an
accredited MD-geneticist. The Company’s first Expert Center was established
earlier this year in Bonn, Germany, to provide the Company’s first testing
service for MODY diabetes (Mature Onset Diabetes of the Young). The Company’s
strategy is to develop molecular diagnostic tools for selected disease areas
with high medical need. IntegraGen’s in-house programs are focused on
neurological disorders, including autism and bi-polar disorder, and metabolic
disorders, such as obesity and type 2 diabetes mellitus.
Founded in July
2000, IntegraGen has 34 employees and is based in the French Genopole of Evry,
near Paris, France, and in Bonn, Germany. More information can be found at
www.integragen.com
About the Autism Genetic Resources Exchange (AGRE) program
The Autism Genetic Resource Exchange (AGRE) is a program of Cure
Autism Now and is supported, in part, by grant MH64547 from the National
Institute of Mental Health to Daniel H. Geschwind (PI).
AGRE is a DNA
repository and family registry, housing a database of genotypic and phenotypic
information available to the entire scientific community. In the fourth edition
of the catalog, there are a total of 436 families currently available for
distribution, 385 of which are multiplex. AGRE and the AGRE Steering Committee
oversees protocols for phlebotomy, ADI-R and ADOS-G evaluations, data collection
and storage, pedigree production and the distribution of quality controlled DNA,
cell line and serum samples. The AGRE Program is located in Los Angeles, CA.
More information can be found at
http://www.agre.org/program/intro.cfm?do=program
About autism
Autism a cognitive
and neurobehavioural disorder, within a spectrum of pervasive developmental
disorders. It is usually a lifelong disability, although, in some cases with
intensive treatment, this is not always the case. The condition affects the way
a person communicates and relates to people around them, reducing their capacity
to understand other people’s feelings and to develop effective relationships .
According to the World Health Organisation, the prevalence of autism varies
considerably, reflecting differences in ascertainment and diagnosis rates,
ranging from 0.7 to 21.1 per 10,000 children. In recent years, systematic
family and twin studies have shown that genetic factors play an important role
in autism. About 3% of siblings of a child with autism also develop autism, a
rate 50 to 100 times greater than the rate in the general population. The twin
concordance rate for autism spectrum disorder in identical twins is around 90%,
much higher than in non-identical twin pairs, supporting the role of genetics.
However, the genetics of autism are complex and it appears likely that several
overlapping sets of predisposing genes contribute to overall susceptibility.
Media enquiries
Northbank Communications
Dr Rebecca Todd, Senior Account Manager
Tel: +44 (0)20 7886 8157
Mobile: +44 (0)7801 573073
E-mail:
r.todd@northbankcommunications.com
At IntegraGen
Dr Jan Mous, CEO
Tel: +33 (0)1 60 91 09 00
Email:
jan.mous@integragen.com
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