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- Posted Wednesday May 13, 2015
TGen study matches infant stiff-joint syndromes to possible genetic origins
More than 50 rare but specific disorders and syndromes characterized, leading to new possible treatments
PHOENIX, Ariz. - May 13, 2015 - A study led by
the Translational
Genomics Research Institute (TGen) has for the first time
matched dozens of infantile diseases and syndromes involving muscle
weakness and stiff joints to their likely genetic origins.
The study, in association with the University of British Columbia
and BC Children's Hospital Vancouver, was published this month
(May) in the American Journal of Medical Genetics. The
study's goal is to better enable physicians and geneticists to
advance new treatments that might help these children.
"It's amazing to us how diverse and complex the underlying
genetics is for all of these diseases or syndromes," said Dr. Lisa
Baumbach-Reardon, a TGen Associate Professor and the study's
co-senior author. "A better understanding of disorders with
contractures at birth and their associated genetics is
critical for accurate diagnosis and optimal treatment."
The study describes over 50 of the more than 400 rare, but
specific, disorders associated with multiple muscle contractures
and stiff joints among newborns. They affect arms, legs, torsos and
other parts of the body, often in combinations.
These more than 50 disorders are called "X-linked" syndromes,
because the genes that cause them are on the X chromosome.
Unaffected mothers can pass them on to their children, most often
to their sons.
The study, or compilation of studies, identified 20 different
genes associated with three categories of these more than 50
syndromes:
• One category represented more than 20
syndromes in which the responsible X-linked genes have been
identified.
• A second category represented seven distinct
reports consistent with X-linkage and present with
contractures.
• A third category represented an additional 20
syndromes with reported contractures that are suspected to be
X-linked.
"Clearly, there are many different causes of stiff joints in
newborns," said Dr. Judith Hall, Emerita Professor in the
Departments of Pediatrics andMedical Genetics at the
University of British Columbia and BC Children's Hospital, and the
study's other co-senior author.
"We wanted to bring together the clinical description of each of
these syndromes, and match them to genes, the biochemistry of
genes, and the cellular pathways, in order to identify potential
therapies," said Dr. Hall, one of the world's leading experts in
describing birth defects.
This ontology - or search of all medical literature - is believed
to be the most comprehensive ever undertaking for these
diseases.
Dr. Jesse Hunter, a TGen Research Assistant Professor and the
study's lead author, said understanding how to potentially
intervene and prevent stiff joints during pregnancy are
fundamental.
"Contractures can develop at any age as a result of neuromuscular
dysfunction, or limitation of movement, but muscle innervation and
movement in utero is particularly critical for normal joint
development," Dr. Hunter said.
The study, Review of X-Linked Syndromes with Arthrogryposis or
Early Contractures - Aid to Diagnosis and Pathway Identification,
concludes: "It is our hope that with advances in clinical
evaluation, next generation sequencing, and bioinformatics tools,
that these syndromes will (all) have identifiable molecular
etiologies (causes) in the near future."
Major funding for this study was provided by TGen, the Muscular
Dystrophy Association, and the Flinn Foundation, with additional
funding from the TGen-Duke Biomedical Futures Program, the Helios
Education Foundation, and the Freeport-McMoRan Copper & Gold
Foundation.