|
| |
 |
October 16, 2002
Members
Joubert Syndrome Foundation
Re: Breaking Research News
Dear Friends:
It is a pleasure for me to report that scientists from
the University of Missouri (Drs. Braddock, Farmer,
Maria, and Miles) and the University of California San
Diego (Dr. Wynshaw-Boris) have teamed up to study
Joubert syndrome. Importantly, the National Institutes
of Health (NIH) will fund the proposed research.
Dr. Wynshaw-Boris is investigating the genetic and
biochemical pathways that are important in brain
development. A major effort is to study the role of
genes in the development of the junction between the
midbrain and hindbrain (isthmus), and cerebellum.
Specific tools have been developed to inactivate genes
in these brain regions and to study the consequences.
Dr. Wynshaw-Boris and University of Missouri
investigators were recently awarded a grant from NIH to
extend research in the mouse to attempt to model Joubert
syndrome, and to better define features of the disease
in humans.
Common clinical features of Joubert syndrome are low
muscle tone, delay in development, balance problems, and
the molar tooth sign detected on MRI of the brain. Other
associated abnormalities include breathing problems, eye
problems, and kidney disease. Uncommon abnormalities
include polydactyly, macrocephaly, soft tissue tongue
tumors, and many others. In 1998 and 2002, Dr. Maria
chaired scientific symposia on Joubert syndrome that
were funded by the NIH and co-sponsored by the National
Institute of Neurologic Disorders and Stroke, the Office
of Rare Diseases, and the Joubert Syndrome Foundation.
The expert panels in both workshops produced specific
recommendations and defined future research directions
that our research proposes to address.
The role of genetics in Joubert syndrome is
indisputable; however, the location of the relevant
genes, their contribution to disease onset and
progression and the possible associated role of
epigenetic factors is as yet unknown. In addition, a
number of related disorders of hindbrain development
such as Arima-Dekaban, Senior-Loken Syndrome, Varadi
syndrome, or COACH have made the study of Joubert
syndrome problematic. Lack of animal models, incomplete
characterization of clinical features, as well as
limitations resulting from geographic distribution of
the study population, staffing, funding, and the
feasibility of collecting a large number of families
have hampered previous investigations.
The overall goal of our research is to expand the
understanding of the cause, diagnosis, and management of
Joubert syndrome. Our specific aims are:
Specific Aim 1 will produce mouse mutants with
inactivation of genes that participate in several
aspects of midbrain-hindbrain development. It is
anticipated that some of these mutants will share
neuropathological features with Joubert syndrome. If so,
such animal models and mutant mice will help focus the
search for candidate genes for Joubert syndrome.
Specific Aim 2 will establish a national Registry
to inform research studies in Joubert syndrome.
Collection of data for a sufficient number of families
should provide adequate power of analysis for studies of
clinical features and of genetic etiology. The Registry
will: (a) identify and recruit affected individuals with
Joubert syndrome; (b) collect clinical and radiological
data including pedigree information, medical records
concerning diagnosis and treatment, clinical features,
and MRI data; (c) ensure that blood samples are
forwarded to the Genetics Core directed by Dr. Phil
Chance at the University of Washington in Seattle; and
(d) analyze clinical data as a means to stratify the
sample for linkage analyses in candidate regions.
Specific Aim 3 will clarify the heterogeneity
within the Joubert syndrome diagnosis by characterizing
the physical phenotype, family history, language and
neuro-psychological features. We will determine the
relative frequencies of system involvement in Joubert
syndrome and what clinical (eye, face, brain, kidney,
liver, finger, behavioral, neuropsychological) and
radiological features cluster in affected sibs. Studies
in Aim 3 will assist with the development of practice
guidelines in the evaluation and monitoring of children
with Joubert syndrome and related conditions.
In summary, we have secured Federal funding to advance
our understanding of Joubert syndrome and to establish a
national registry that you will be hearing more about
from the Foundation in coming months. I am especially
grateful to all families who have actively participated
in past clinical studies and I look forward to keeping
you updated on progress with our research.
Sincerely yours,
Bernard L. Maria, MD, MBA
Children's Miracle Network Distinguished Professor of
Child Health
Professor of Pediatrics, Neurology, and Neuroscience
Chairman, Department of Child Health
Pediatrician-in-Chief of Children's Hospital
University of Missouri Health Care
cc. Dr. Wynshaw-Boris
Principal Investigator
Back to Physician
Research Page |
|
|
Printer friendly version |
| |
|
The views expressed do
not necessarily reflect those of the donors. The articles,
announcements, and resources included on this website are
for information only and should not be considered as medical
advice. Please always consult your physician for medical
advice. The Joubert Syndrome Foundation & Related Cerebellar
Disorders does not endorse any product, service, or theory
referred to on the website.
|
|
|