With CMTA support of $210,000, researchers led by Andrea Cortese, MD, PhD, at University College London (UCL) Queen Square Institute of Neurology are using advanced long-read DNA sequencing to uncover the genetic causes of CMT that remain undiagnosed after standard testing.
October 2025 Update
In the first six months, the team reanalyzed short-read data from more than 1,400 people with CMT, applying updated tools and detailed clinical review to increase the number of confirmed genetic diagnoses. This effort helped define a group of 150 unsolved cases for long-read sequencing.
The team evaluated CGG repeat expansions, a recently recognized type of gene mutation that duplicates a small section of a gene. These changes are invisible to standard genetic testing but can be detected using long-read sequencing. The findings confirmed that this type of mutation can play a role in CMT, leading to genetic confirmation for seven community members. These seven individuals had previously been unable to receive genetic confirmation using conventional genetic testing methods.
Early long-read sequencing results revealed previously hidden mutations in the SORD gene, a very difficult gene to test for, showing how long-read sequencing can solve complex CMT cases. The study also contributed to the international effort that verified newly discovered KCTD11 gene mutations causing Recessive Intermediate CMT E (CMTRIE), expanding CMT’s genetic landscape and bringing long-awaited answers to community members.
Together, these findings show how long-read sequencing can close persistent diagnostic gaps and deepen understanding of the genetic foundations of CMT.
