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Novel MORC2 variants in Charcot–Marie–Tooth disease type 2Z: genetic and functional insights
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DOI：10.3389/fmed.2026.1864944.png)
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Abstract
En 中文
BackgroundCharcot–Marie–Tooth disease type 2Z (CMT2Z) is an uncommon inherited condition characterized by autosomal dominant inheritance. It is marked by axonal neuropathy; leading to progressive muscle weakness; cramps; and sensory loss. MORC2 is one of the candidate pathogenic genes for CMT2Z.MethodsHere; we enrolled two families affected by Charcot–Marie–Tooth (CMT) disease; with both families having probands who exhibit distal lower limb weakness. Whole-exome sequencing (WES) was used to explore the genetic lesion.ResultsTwo heterozygous variants (NM_001303256; c.34G > C;p.A12P; NM_001303256; c.848G > A;p.R283H) of MORC2 gene were found. The c.848G > A;p.R283H variant is rare; and the c.34G > C;p.A12P variant has not been reported before. Functional studies revealed that the c.848G > A;p.R283H variant resulted in reduced transcription of the MORC2 gene. The c.34G > C;p.A12P variant did not impact MORC2 gene transcription; yet it influenced the protein’s half-life and stability. Based on genetic analysis; two probands were subsequently diagnosed with CMT2Z.ConclusionOur research contributed to the genetic assessment and guidance for these families; reinforcing the notion that MORC2 is a potential causative gene for CMT2Z.
Keywords:
variant
WES
axonal neuropathy
CMT2Z
MORC2
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