There are many rare disorders and while they don't get much attention from the public at large, they are life-changing for the families and people that are affected, and it's still important to study these diseases. They can also offer insight into biology; when there is dysfunction, researchers often gain crucial knowledge about how things normally function. New work has traced a rare genetic disorder to a causative gene in one patient. Opitz C syndrome impacts 60 people in the world, causing severe disabilities. This finding is a solid foundation on which to lie future work determining the mechanisms underlying the disease, which is the only way to develop treatments. Another benefit is the new possibility of genetic and prenatal testing for this disorder. You can see a patient with Opitz C in the following video.
Researchers at the Group on Human Molecular Genetics of the University of Barcelona and the Biomedical Research Networking Center of Rare Diseases (CIBERER), led by professors Daniel Grinberg and Susana Balcells, have published their findings in the journal Scientific Reports. The mutation they found is in a gene called MAGEL2. That gene is in the region of mutations causative for another disorder, Prader-Willi. It also coincides with a mutation identified in a patient with Schaaf-Yang syndrome - another ultra-rare disease of about 50 people in the world. These diseases have very similar pathologies including symptoms like learning disabilities, psychomotor dysfunction and trigonocephaly (triangular forehead) and are diagnosed on a case-by-case basis. This new finding expands our understanding of these unusual 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," said Professor Daniel Grinberg, a member of the Institute of Biomedicine at the University of Barcelona (IBUB), the Research Institute of Sant Joan de Déu (IRSJD) and CIBERER.
"Consequently, from a genetic diagnosis perspective this patient initially diagnosed with Opitz C in Catalonia would correspond to the group of patients with Schaaf-Yang syndrome," said Grinberg.
The researchers applied massive sequencing that covers both the exome - expressed genes, and the genome - all of the genetic information. There is now a way to begin to study how to treat the disorder. "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," said Luis Serrano, director of CRG.
"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," commented Susana Balcells, tenured lecturer at the UB and a member of IBUB and CIBERER.
"All these clinical doubts 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 create them," concluded Balcells.
A lot of collaborative effort went into this work. Meetings between expert researchers and affected families were essential to the findings, and patients in the same geopgraphical area were even examined by the same physician. Interestingly, crowd funding enabled this research through PRECIPITA (Spanish Foundation for Science and Technology, FECYT).