PMID- 32896048
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20220107
IS  - 1468-1331 (Electronic)
IS  - 1351-5101 (Linking)
VI  - 27
IP  - 12
DP  - 2020 Dec
TI  - Bi-allelic mutations in EGR2 cause autosomal recessive demyelinating neuropathy 
      by disrupting the EGR2-NAB complex.
PG  - 2662-2667
LID - 10.1111/ene.14512 [doi]
AB  - BACKGROUND AND PURPOSE: Mutations in the early growth response 2 gene (EGR2) 
      cause demyelinating, but also axonal, neuropathies differing in severity and age 
      of onset. Except for one family, all reported cases have autosomal dominant 
      inheritance and mutations are localized within the three zinc finger (ZNF) 
      DNA-binding domain. The aim of this study was to provide a clinical and molecular 
      analysis of a novel recessive mutation in EGR2. METHODS: Clinical and 
      electrophysiological assessments of three affected patients, from a 
      consanguineous family, were performed. Genetic analyses of EGR2 were carried out 
      by Sanger sequencing. Functional effects of clinical recessive mutations were 
      assessed using a mammalian two-hybrid assay. RESULTS: A novel missense mutation 
      (c.791C>T; p.P264L) in the homozygous state was detected outside the ZNF domains 
      of the EGR2 gene. Three affected siblings presented with distal demyelinating 
      polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and 
      trigeminal neuralgia. Respiratory compromise and cranial nerve dysfunction were 
      also found. Our data indicate that the p.P264L mutation prevents interaction of 
      EGR2 transcription factor with NAB corepressors, suggesting that a disruption of 
      the NAB-EGR2 protein interactions can result in dramatic neuropathy. CONCLUSION: 
      Mutations in, or next to, the R1 domain of EGR2 should be considered with extreme 
      caution for genetic counseling, since these could cause a severe neuropathy with 
      an autosomal recessive manner of transmission.
CI  - (c) 2020 European Academy of Neurology.
FAU - Lupo, V
AU  - Lupo V
AUID- ORCID: 0000-0002-3774-9854
AD  - Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, 
      Centro de Investigacion Principe Felipe (CIPF), Valencia, Spain.
AD  - Rare Diseases Joint Units, IIS La Fe-CIPF, Valencia, Spain.
FAU - Won, S
AU  - Won S
AD  - Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
FAU - Frasquet, M
AU  - Frasquet M
AUID- ORCID: 0000-0001-7206-5362
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital Universitari i 
      Politecnic La Fe, Valencia, Spain.
AD  - Neuromuscular and Ataxias Research Group, Instituto de Investigacion Sanitaria La 
      Fe, Valencia, Spain.
FAU - Schnitzler, M S
AU  - Schnitzler MS
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - Komath, S S
AU  - Komath SS
AUID- ORCID: 0000-0002-0491-7102
AD  - Jawaharlal Nehru University, New Delhi, India.
FAU - Pascual-Pascual, S I
AU  - Pascual-Pascual SI
AD  - Neuropediatrics Service, Hospital Universitario La Paz, Madrid, Spain.
FAU - Espinos, C
AU  - Espinos C
AUID- ORCID: 0000-0003-4435-1809
AD  - Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, 
      Centro de Investigacion Principe Felipe (CIPF), Valencia, Spain.
AD  - Rare Diseases Joint Units, IIS La Fe-CIPF, Valencia, Spain.
FAU - Svaren, J
AU  - Svaren J
AUID- ORCID: 0000-0003-2963-7921
AD  - Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - Sevilla, T
AU  - Sevilla T
AUID- ORCID: 0000-0003-4716-2667
AD  - Rare Diseases Joint Units, IIS La Fe-CIPF, Valencia, Spain.
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital Universitari i 
      Politecnic La Fe, Valencia, Spain.
AD  - Neuromuscular and Ataxias Research Group, Instituto de Investigacion Sanitaria La 
      Fe, Valencia, Spain.
AD  - Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), 
      Valencia, Spain.
AD  - Department of Medicine, Universitat de Valencia, Valencia, Spain.
LA  - eng
GR  - PI19/00142/Instituto de Salud Carlos III/
GR  - PI16/00403/Instituto de Salud Carlos III/
GR  - PROMETEO/2018/135/Generalitat Valenciana/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200927
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (EGR2 protein, human)
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Charcot-Marie-Tooth Disease/*genetics
MH  - Early Growth Response Protein 2/*genetics
MH  - Homozygote
MH  - Humans
MH  - Mutation
MH  - Transcription Factors/genetics
OTO - NOTNLM
OT  - EGR2
OT  - NAB
OT  - autosomal recessive
OT  - demyelinating neuropathy
OT  - scoliosis
EDAT- 2020/09/09 06:00
MHDA- 2021/06/11 06:00
CRDT- 2020/09/08 05:27
PHST- 2020/04/28 00:00 [received]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/09/09 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2020/09/08 05:27 [entrez]
AID - 10.1111/ene.14512 [doi]
PST - ppublish
SO  - Eur J Neurol. 2020 Dec;27(12):2662-2667. doi: 10.1111/ene.14512. Epub 2020 Sep 
      27.