Opitz C syndrome is a genetic disease described for the
first time in 1969 by John M. Opitz. The genetic bases of this ultra-minority disease are still unknown. It causes severe
disabilities in patients and has been diagnosed in three people in the
Iberian Peninsula, and 60 people in the world.
A team led by the
professors Daniel Grinberg and Susana Balcells, from the Group on Human
Molecular Genetics of the University of Barcelona and the Biomedical
Research Networking Center of Rare Diseases (CIBERER) has now identified
a gene that causes the Opitz C syndrome in the only patient in
Catalonia diagnosed with this severe congenital disease.
‘The gene that causes Opitz C syndrome in the only patient diagnosed with this ultra-rare disorder has been identified.’
scientific advance is a first step to discover the genetic bases of this
syndrome which, so far, does not offer treatment possibilities,
prenatal diagnosis or genetic counseling.
The new study, published in the journal Scientific Reports
has the participation of several researchers at the CRG, including
members of the Genomic and Epigenomic Variation in Disease laboratory,
the genomics unit, and the bioinformatics unit. It also had the
participation of John M. Opitz (University of Utah, United States),
Giovanni Neri (Catholic University of the Sacred Heart, Italy) and
experts at the Department of Clinical and Molecular Genetics of the
University Hospital Vall d'Hebron (VHIR).
Opitz C syndrome: rare but not invisible
It is generally
thought that its origin is caused by the apparition of dominant
-maternally silenced- novo mutations. At the moment, the diagnose is
clinical and it is based on the symptomatology presented on patients
with different degrees (trigonocephaly, learning disability, psychomotor
disability, etc.) and which, in lots of cases, coincides with similar
minority pathologies such as the syndromes of Schaaf-Yang, Bohring-Opitz
In the new study, the experts described for the first time, the
existence of a novo mutation -p.Q638*- located in the gene MAGEL2 of the
only diagnosed person with Opitz C syndrome in Catalonia. Identifying
this mutation, found in the Prader-Willi Region on chromosome 15, widens
the knowledge horizons on genetics and the possibilities for a
diagnosis on these rare diseases.
"The p.Q638* mutation, identified in the gene MAGEL2, coincides with
the one described concurrently and independently in a patient with
Schaaf-Yang syndrome, a new minoritary disease affecting fifty people in
the world. The first cases were described on a scientific bibliography
in 2013 by the team of Professor Christian Schaaf, from the Baylor
College of Medicine, Houston", says Professor Daniel Grinberg, member of
the Institute of Biomedicine of the University of Barcelona (IBUB), the
Research Institute of Sant Joan de Déu (IRSJD) and CIBERER.
"Consequently, from a genetic diagnosis perspective -says DanieL
Grinberg- this patient initially diagnosed with Opitz C in Catalonia
would correspond to the group of patients with Schaaf-Yang syndrome"
Genetics will define the limits of rare diseases
Identifying the genes that cause a disease is a breakpoint to
understand the pathology and set new future therapeutic approaches that
improve the quality of life of the patients. In the new study, the teams
of the UB and the CRG applied techniques of DNA massive sequencing
(exome and genome), a powerful methodology that allows identifying
altered genes in each patient.
According to Luis Serrano, director of CRG, "projects like this one
show the important role of genomics in the future of medicine and the
way on which we diagnose and treat diseases. To understand the diseases
and offering not only a diagnosis but also approaches to possible
treatments is very relevant in minority diseases. It is a satisfaction
for the CRG to contribute with our knowledge and advanced technologies
in a project that gives hope to a vulnerable collective" concluded the
Susana Balcells, tenured lecturer at the UB and also member of IBUB
and CIBERER, added "what we can see from a clinical symptomatology view
in these kinds of diseases which are so hard to study and diagnose, is
far from the initial molecular defect that generates the disease".
"All these clinical doubts -continued Balcells- will be solved with
genetics, which will define the limits of these rare diseases and will
ease the scientific consensus on the diagnosis and genetic causes that