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| Hereditary neuropathy or pain disorder v8.26 | EGR2 | Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are 2 unrelated families reported in literature with biallelic EGR2 missense variants, as well as 1 case reported with a homozygous deletion of the EGR2 enhancer, where probands presented with a congenital neuropathy. The more common dominant CMT disease is caused by variants within three-ZNF DNA-binding domains of EGR2; the recessive variants are the only ones reported outside of that domain (PMID: 40262821 Cavalcanti et al., 2025). EGR2 knockout mouse models support the association, as they display disrupted hindbrain segmentation and development (phenotype not seen in het knockouts). Hence, the MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Comment on mode of inheritance: There are 2 unrelated families reported in literature with biallelic EGR2 missense variants, as well as 1 case reported with a homozygous deletion of the EGR2 enhancer, where probands presented with a congenital neuropathy. The more common dominant CMT disease is caused by variants within three-ZNF DNA-binding domains of EGR2; the recessive variants are the only ones reported outside of that domain (PMID: 40262821 Cavalcanti et al., 2025). EGR2 knockout mouse models support the association, as mutant mice display disrupted hindbrain segmentation and development (phenotype not seen in het knockouts). Hence, the MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.26 | EGR2 | Ida Ertmanska commented on gene: EGR2: Comment on mode of inheritance: There are 2 unrelated families reported in literature with biallelic EGR2 missense variants, as well as 1 case reported with a homozygous deletion of the EGR2 enhancer, where probands presented with a congenital neuropathy. The more common dominant CMT disease is caused by variants within three-ZNF DNA-binding domains of EGR2; the recessive variants are the only ones reported outside of that domain (PMID: 40262821 Cavalcanti et al., 2025). EGR2 knockout mouse models support the association, as they display disrupted hindbrain segmentation and development (phenotype not seen in het knockouts). Hence, the MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.26 | EGR2 | Ida Ertmanska Phenotypes for gene: EGR2 were changed from Charcot-Marie-Tooth, Type 1; Charcot Marie Tooth disease, type 1D, 607678 to Charcot-Marie-Tooth disease, type 1D, MIM:607678; Dejerine-Sottas disease, MIM:145900; Hypomyelinating neuropathy, congenital, 1, MIM:605253 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.25 | EGR2 | Ida Ertmanska Publications for gene: EGR2 were set to 9537424 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.24 | EGR2 | Ida Ertmanska Tag Q3_26_MOI tag was added to gene: EGR2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v8.24 | EGR2 |
Ida Ertmanska changed review comment from: PMID: 32896048 Lupo et al., 2020 3 affected sibs with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. All 3 individuals were homozygous for the c.791C>T; p.P264L variant in EGR2. Variant not present in gnomAD v4. Consanguineous parents (confirmed het) and wt/het sibs unaffected. PMID: 9537424 Warner et al., 1998 Study included 94 neuropathy patients. Only exons of EGR2 were sequenced. Family HOU336 - 3 male sibs affected by a congenital hypomyelinating neuropathy (CHN). They were floppy at birth, had delayed motor milestones, and walked with crutches at the time of report. The c.803T>A, p.Ile268Asn homozygous missense variant was detected in EGR2 - not reported in gnomAD v4. Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage - phenotype not seen in heterozygous +/- mice. Reports of dominant EGR2-related CMT PMIDs: 9537424; 11523566; 17717711; 20513111; 26204789; 27159987; 30481651; 30843326; 31852952 - copied from ClinGen summary. The association between EGR2 and Semidominant Charcot-Marie-Tooth disease was classified as Definitive (Charcot-Marie-Tooth GCEP, Nov 2021). The gene is associated with AD Charcot-Marie-Tooth disease, type 1D, MIM:607678, AD,AR Dejerine-Sottas disease, MIM:145900, and AD,AR Hypomyelinating neuropathy, congenital, 1, MIM:605253 in OMIM; EGR2-related neuropathy, congenital hypomyelinating (biallelic_autosomal) is ranked Definitive in Gene2Phenotype (accessed 28th July 2026).; to: PMID: 32896048 Lupo et al., 2020 3 affected sibs with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. All 3 individuals were homozygous for the c.791C>T; p.P264L variant in EGR2. Variant not present in gnomAD v4. Consanguineous parents (confirmed het) and wt/het sibs unaffected. PMID: 9537424 Warner et al., 1998 Study included 94 neuropathy patients. Only exons of EGR2 were sequenced. Family HOU336 - 3 male sibs affected by a congenital hypomyelinating neuropathy (CHN). They were floppy at birth, had delayed motor milestones, and walked with crutches at the time of report. The c.803T>A, p.Ile268Asn homozygous missense variant was detected in EGR2 - not reported in gnomAD v4. Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage - phenotype not seen in heterozygous +/- mice. PMID: 22522483 Funalot et al., 2012 Female proband with a congenital amyelinating neuropathy; consanguineous parents of Moroccan origin. She presented with hypotonia at birth, EMG showed absence of peripheral response. No EGR2 immunoreactivity seen in Schwann cells. Detected a homozygous 10.7-kilobase-long deletion encompassing a myelin-specific enhancer of EGR2 in the proband (**non-coding regulatory variant**). Reports of dominant EGR2-related CMT PMIDs: 9537424; 11523566; 17717711; 20513111; 26204789; 27159987; 30481651; 30843326; 31852952 - copied from ClinGen summary. The association between EGR2 and Semidominant Charcot-Marie-Tooth disease was classified as Definitive (Charcot-Marie-Tooth GCEP, Nov 2021). The gene is associated with AD Charcot-Marie-Tooth disease, type 1D, MIM:607678, AD,AR Dejerine-Sottas disease, MIM:145900, and AD,AR Hypomyelinating neuropathy, congenital, 1, MIM:605253 in OMIM; EGR2-related neuropathy, congenital hypomyelinating (biallelic_autosomal) is ranked Definitive in Gene2Phenotype (accessed 28th July 2026). |
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| Hereditary neuropathy or pain disorder v8.24 | EGR2 |
Ida Ertmanska changed review comment from: PMID: 32896048 Lupo et al., 2020 3 affected sibs with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. All 3 individuals were homozygous for the c.791C>T; p.P264L variant in EGR2. Consanguineous parents (confirmed het) and wt/het sibs unaffected. PMID: 9537424 Warner et al., 1998 p.I268N homozygous missense variant detected in EGR2. Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage. The association between EGR2 and Semidominant Charcot-Marie-Tooth disease was classified as Definitive (Charcot-Marie-Tooth GCEP, Nov 2021). The gene is associated with AD Charcot-Marie-Tooth disease, type 1D, MIM:607678, AD,AR Dejerine-Sottas disease, MIM:145900, and AD,AR Hypomyelinating neuropathy, congenital, 1, MIM:605253 in OMIM; EGR2-related neuropathy, congenital hypomyelinating (biallelic_autosomal) is ranked Definitive in Gene2Phenotype (accessed 28th July 2026).; to: PMID: 32896048 Lupo et al., 2020 3 affected sibs with distal demyelinating polyneuropathy with severe sensory loss, progressive thoracolumbar scoliosis and trigeminal neuralgia. All 3 individuals were homozygous for the c.791C>T; p.P264L variant in EGR2. Variant not present in gnomAD v4. Consanguineous parents (confirmed het) and wt/het sibs unaffected. PMID: 9537424 Warner et al., 1998 Study included 94 neuropathy patients. Only exons of EGR2 were sequenced. Family HOU336 - 3 male sibs affected by a congenital hypomyelinating neuropathy (CHN). They were floppy at birth, had delayed motor milestones, and walked with crutches at the time of report. The c.803T>A, p.Ile268Asn homozygous missense variant was detected in EGR2 - not reported in gnomAD v4. Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage - phenotype not seen in heterozygous +/- mice. Reports of dominant EGR2-related CMT PMIDs: 9537424; 11523566; 17717711; 20513111; 26204789; 27159987; 30481651; 30843326; 31852952 - copied from ClinGen summary. The association between EGR2 and Semidominant Charcot-Marie-Tooth disease was classified as Definitive (Charcot-Marie-Tooth GCEP, Nov 2021). The gene is associated with AD Charcot-Marie-Tooth disease, type 1D, MIM:607678, AD,AR Dejerine-Sottas disease, MIM:145900, and AD,AR Hypomyelinating neuropathy, congenital, 1, MIM:605253 in OMIM; EGR2-related neuropathy, congenital hypomyelinating (biallelic_autosomal) is ranked Definitive in Gene2Phenotype (accessed 28th July 2026). |
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| Hereditary neuropathy or pain disorder v8.24 | EGR2 | Ida Ertmanska reviewed gene: EGR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 9537424, 32896048; Phenotypes: Charcot-Marie-Tooth disease, type 1D, MIM:607678, Dejerine-Sottas disease, MIM:145900, Hypomyelinating neuropathy, congenital, 1, MIM:605253; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hereditary neuropathy or pain disorder v0.1 | EGR2 |
Ellen McDonagh gene: EGR2 was added gene: EGR2 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,Illumina TruGenome Clinical Sequencing Services,London North GLH,Expert list,Emory Genetics Laboratory,UKGTN,Expert Review Green,South West GLH,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: EGR2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: EGR2 were set to 9537424 Phenotypes for gene: EGR2 were set to Charcot-Marie-Tooth, Type 1; Charcot Marie Tooth disease, type 1D, 607678 |
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