JUL 06, 2017 6:49 PM PDT

Cause of Carey-Fineman-Ziter Syndrome, Potential Treatment ID'ed

WRITTEN BY: Carmen Leitch

Investigators have found the genetic disorder underlying a rare muscle disease, Carey-Fineman-Ziter (CFZS). Patients suffer facial weakness and have a small or retracted chin, a cleft palate and curvature of the spine (scoliosis), along with other symptoms. Mutations in the gene MYMK, which encodes for the protein myomaker, cause CFZS. Myomaker acts in development to promote the fusion of muscle stem cells (myoblasts) into muscle fibers (myotubes), as well as playing a role in muscle cell regeneration after an injury. The work has been reported in Nature Communications.

"Advances in genomics technology and the power of team science have enabled us to identify the cause of this very rare disease 35 years after it was first described by Dr. John Carey and colleagues from the University of Utah," said National Institutes of Health Director Francis S. Collins, M.D., Ph.D., who is a co-author of the report. The video above features Dr. Carey and a family that is affected by CFZS.

"This discovery will improve physicians' ability to diagnose this disease and offer families accurate genetic counseling and treatment," said co-lead author Irini Manoli, M.D., Ph.D., a physician scientist and staff clinician in the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute (NHGRI). Diagnosing this disease has been confounded by another rare disorder called Moebius syndrome.

Determining that cell-cell fusion disorders can lead to congenital myopathies (inherited muscle disease) opens a new avenue of exploration for therapeutics not only for CFZS, but for other muscular diseases and muscle regeneration, said Dr. Manoli. ”In addition," she said, "this rare genetic syndrome provides novel insights into the effects of muscle development on craniofacial and skeletal bone formation."

The graphic depicts normal myoblasts (early muscle cells with a single nucleus) fusing together to form muscle cells with more than one nucleus. The cascade is disrupted in Carey-Fineman-Ziter syndrome, because of a defect in the membrane protein, myomaker, which is required for cell-cell fusion / Credit: Darryl Leja, NHGRI

This work was aided by 63 patients with Moebius syndrome and other facial paralysis diseases, who came to the NIH clinical center for detailed evaluations. Beyond that, extensive genetic analysis was done to identify genetic mutations that are linked to CFZS. The researchers narrowed down the candidates by finding a single mutated gene that was common to three families affected by Moebius. 

The scientists turned to animal models to follow up on this gene, MYMK - myomaker. A mouse, edited so that the MYMK gene was ablated, and a zebrafish whose MYMK gene was altered with the CRISPR-Cas9 genome editing tool confirmed the suspicions of the researchers. The experimental zebrafish had jaw deformities, and the mutant mice had severe muscle dysfunction. The investigators were actually able to treat the zebrafish and correct the deformity, so there is now hope for new treatments. This work will also of course help to diagnose the disease in other patients.

 

Sources: AAAS/Eurekalert! via NIH/NHGRI, eLife, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 27, 2021
Cell & Molecular Biology
Lasers Stimulate Stem Cells to Grow & Specialize Faster
OCT 27, 2021
Lasers Stimulate Stem Cells to Grow & Specialize Faster
Our body can only repair so much damage or injury, so treatments that can regenerate damaged or dead tissues may be very ...
NOV 09, 2021
Health & Medicine
How to Search the Cyagen Knockout Catalog Models Resource?
NOV 09, 2021
How to Search the Cyagen Knockout Catalog Models Resource?
The Cyagen Knockout Catalog Models repository provides researchers in the Americas and Europe with ready-to-use knockout ...
NOV 05, 2021
Genetics & Genomics
Solution to a Pigeon Genetic Mystery Provides Insight Into Development
NOV 05, 2021
Solution to a Pigeon Genetic Mystery Provides Insight Into Development
This photo by Sydney Stringham shows the domestic pigeons that were bred by the researchers for this research.
NOV 18, 2021
Genetics & Genomics
Some Gene Isoforms are Exclusively Expressed in the Brain
NOV 18, 2021
Some Gene Isoforms are Exclusively Expressed in the Brain
For simplicity's sake, it's easy to think of the genome as a set of instructions that cells use to create the pr ...
NOV 19, 2021
Cell & Molecular Biology
Viral RNA Can Hijack the Host by Assuming a tRNA-Like Structure
NOV 19, 2021
Viral RNA Can Hijack the Host by Assuming a tRNA-Like Structure
Many viruses have genomes made of RNA. In human cells, messenger RNA (mRNA) molecules act as intermediates; cellular mac ...
NOV 21, 2021
Genetics & Genomics
Crucial Developmental Genes Found to Still be Active in Adulthood
NOV 21, 2021
Crucial Developmental Genes Found to Still be Active in Adulthood
Hox genes play a critical role in mapping the development of multicellular organisms. This group of genes is also expres ...
Loading Comments...