SUMMARY:
Novel or very rare variants in MYO9B are associated with CMT2 and isolated OA.
TITLE:
Mutations in MYO9B are associated with CMT2 neuropathies and isolated optic atrophy
DESCRIPTION:
CONCLUSION: Novel or very rare variants in MYO9B are associated with CMT2 and isolated OA.
CONTENT:
Eur J Neurol. 2022 Oct 19. doi: 10.1111/ene.15601. Online ahead of print.
ABSTRACT
OBJECTIVE: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders caused by mutations in at least 100 genes. However, approximately 60% of cases with axonal neuropathies (CMT2) still remain without a genetic diagnosis. We aimed at identifying novel disease genes responsible for CMT2.
METHODS: We performed WES and targeted NGS panel analyses on a cohort of CMT2 families with evidence for autosomal recessive inheritance. We also performed functional studies to explore the pathogenetic role of selected variants.
RESULTS: We identified rare, recessive variants in the MYO9B (Myosin IX) gene in two families with CMT2. MYO9B has not been yet associated with a human disease. MYO9B is an unconventional single-headed processive myosin motor protein with signaling properties, and, consistent with this, our results indicate that a variant occurring in the MYO9B motor domain impairs protein expression level and motor activity. Interestingly, a Myo9b-null mouse has degenerating axons in their sciatic nerves and optic nerves, indicating that MYO9B plays an essential role in both PNS and CNS axons, respectively. The degeneration observed in the optic nerve prompted us to screen for MYO9B mutations a cohort of patients with optic atrophy (OA). Consistent with this, we found compound heterozygous variants in one case with isolated OA.
CONCLUSION: Novel or very rare variants in MYO9B are associated with CMT2 and isolated OA.
PMID:36260368 | DOI:10.1111/ene.15601
SOURCE:
European journal of neurology
TAGS:
MYO9B
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2022-10-19T15:40:27Z
DATE – DOI: 2022-10-19T15:40:27Z
DATE – PUBMED: 2022 Oct 19
DATE OUTPUT MATCHED: True
DATE – ADDED:
Wed, 19 Oct 2022 06:00:00 -0400
DATE – RETRIEVED:
10/19/22 01:03PM
2022-10-19T13:03:07-04:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:36260368,doi:10.1111/ene.15601
PUBMED ID:
pubmed:36260368
DOI:
10.1111/ene.15601
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36260368/
LINK – DOI:
https://doi.org/10.1111/ene.15601
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1111/ene.15601
REFERENCES:
CMT Treatment Report, Urgent Research, 2022-10-19T13:03:07-04:00, https://www.cmttreatmentreport.com.
