SUMMARY:
MORC2 mutations are associated with autosomal dominant CMT and with adult late onset proximal motor neuropathy.
TITLE:
Expanding the phenotypic variability of MORC2 gene mutations: from Charcot Marie tooth disease to late-onset pure motor neuropathy
DESCRIPTION:
MORC2 gene encodes a ubiquitously expressed nuclear protein involved in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous mutations in MORC2 gene have been associated with a spectrum of disorders affecting the peripheral nervous system such as Charcot-Marie-Tooth (CMT2Z), spinal muscular atrophy-like (SMA-like) with or without cerebellar involvement, and a developmental syndrome associated with impaired growth, craniofacial dysmorphism and axonal neuropathy (DIGFAN…
CONTENT:
Hum Mutat. 2022 Jul 29. doi: 10.1002/humu.24445. Online ahead of print.
ABSTRACT
MORC2 gene encodes a ubiquitously expressed nuclear protein involved in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous mutations in MORC2 gene have been associated with a spectrum of disorders affecting the peripheral nervous system such as Charcot-Marie-Tooth (CMT2Z), spinal muscular atrophy-like (SMA-like) with or without cerebellar involvement, and a developmental syndrome associated with impaired growth, craniofacial dysmorphism and axonal neuropathy (DIGFAN syndrome). Such variability in clinical manifestations associated with the increasing number of variants of unknown significance detected by next-generation sequencing constitutes a serious diagnostic challenge. Here we report the characterization of an in vitro model to evaluate the pathogenicity of variants of unknown significance based on MORC2 overexpression in a neuroblastoma cell line SH-EP or cortical neurons. Likewise, we show that MORC2 mutants affect survival and trigger apoptosis over time in SH-EP cell line. Furthermore, overexpression in primary cortical neurons increases apoptotic cell death and decreases neurite outgrowth. Altogether, these approaches establish the pathogenicity of two new variants p.Gly444Arg and p.His446Gln in three patients from two families. These new mutations in MORC2 gene are associated with autosomal dominant CMT and with adult late onset proximal motor neuropathy, further increasing the spectrum of clinical manifestations associated with MORC2 mutations. This article is protected by copyright. All rights reserved.
PMID:35904125 | DOI:10.1002/humu.24445
SOURCE:
Human mutation
TAGS:
MORC2
CATEGORY:
Research
SUBCATEGORY:
n/a
DATE – PUBLISHED:
2022-07-29T10:09:41Z
DATE – DOI: 2022-07-29T10:09:41Z
DATE – PUBMED: 2022 Jul 29
DATE OUTPUT MATCHED: True
DATE – ADDED:
Fri, 29 Jul 2022 06:00:00 -0400
DATE – RETRIEVED:
07/29/22 01:51PM
2022-07-29T13:51:35-04:00
FEATURED IMAGE:
Media Uploaded (image/png)
IDENTIFIER:
pmid:35904125,doi:10.1002/humu.24445
PUBMED ID:
pubmed:35904125
DOI:
10.1002/humu.24445
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/35904125/
LINK – DOI:
https://doi.org/10.1002/humu.24445
LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/humu.24445
REFERENCES:
CMT Treatment Report, Urgent Research, 2022-07-29T13:51:35-04:00, https://www.cmttreatmentreport.com.