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Hereditary neuropathy NOT PMP22 copy number

Gene: MME

Green List (high evidence)

MME (membrane metalloendopeptidase)
EnsemblGeneIds (GRCh38): ENSG00000196549
EnsemblGeneIds (GRCh37): ENSG00000196549
OMIM: 120520, Gene2Phenotype
MME is in 3 panels

9 reviews

Sarah Leigh (Genomics England Curator)

The mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 1:08 p.m. | Last Modified: 14 Mar 2022, 1:08 p.m.
Panel Version: 1.88

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Heterozygous variants have been identified in >10 individuals with late-onset CMT2T. However, some variants have been found in control databases and family studies indicate incomplete penetrance, suggesting heterozygous variants only confer susceptibility. Nonetheless, sufficient cases have been reported in literature and both MOIs are listed in OMIM for this phenotype, and so inclusion of monoallelic inheritance on this panel will first be flagged for GMS review.
Created: 14 Dec 2021, 3:23 p.m. | Last Modified: 14 Dec 2021, 3:23 p.m.
Panel Version: 1.78

Lindsey Vialard (Central and South GLH)

Green List (high evidence)

Comment on mode of inheritance: Mode of inheritance AR and AD.
Auer-Grumbach et al 2016, AJHG Sep 1;99(3):607-623, PMID 27588448: "In this study, we show that heterozygous mutations in MME predispose individuals to late-onset axonal neuropathies". Senderek et al 2020, Neurology Dec 15;95(24):e3163-e3179, PMID 33144514:"MME variants can act as completely penetrant recessive alleles but also confer dominantly inherited susceptibility to axonal neuropathies in an aging population."
Created: 9 Dec 2021, 4:39 p.m. | Last Modified: 9 Dec 2021, 4:39 p.m.
Panel Version: 1.68

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Variants in this GENE are reported as part of current diagnostic practice

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Helen Brittain (Genomics England Curator)

Comment when marking as ready: Sufficient cases, appropriate phenotype. Adult onset neuropathy.
Created: 6 Jul 2018, 8:36 a.m.
Comment on list classification: !0 cases in original report, unrelated with a range of LOF variants. Now further feedback on positive diagnoses. Sufficient evidence for a green rating.
Created: 6 Jul 2018, 8:36 a.m.

Louise Daugherty (Genomics England Curator)

I don't know

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 5 p.m.
Comment on phenotypes: added OMIM phenotype
Created: 11 Apr 2018, 2:54 p.m.

Ellen McDonagh (Genomics England Curator)

Comment on publications: PMID: 26991897 - 10 Japanese patients reported as homozygous for potential loss-of-function mutations, all with late-onset axonal neuropathy. PMID: 27588448 - heterozygous rare loss-of-function and missense mutations in MME identified in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. Some of these variants had incomplete penetrance and were found a low frequency in allele frequency databases. "MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment."
Created: 15 Mar 2017, 12:51 p.m.

Alice Gardham (Genomics England)

Green List (high evidence)

Further patient identified through 100,000 Genomes Cohort
Created: 19 Jan 2017, 10:52 a.m.

Ellen Thomas (Genomics England Curator)

Green List (high evidence)

New evidence - consider adding to panel at next review.
Created: 17 Oct 2016, 2:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • London North GLH
  • NHS GMS
  • NHS GMS
  • London North GLH
  • Expert Review Green
Phenotypes
  • Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017
Tags
adult-onset
OMIM
120520
Clinvar variants
Variants in MME
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Mar 2022, Gel status: 3

Removed Tag, Removed Tag, Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q4_21_expert_review was removed from gene: MME. Tag Q4_21_MOI was removed from gene: MME. Tag Q4_21_NHS_review was removed from gene: MME.

14 Mar 2022, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene MME was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

14 Dec 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q4_21_expert_review tag was added to gene: MME.

14 Dec 2021, Gel status: 3

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: MME was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

14 Dec 2021, Gel status: 3

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag adult-onset tag was added to gene: MME. Tag Q4_21_MOI tag was added to gene: MME.

14 Dec 2021, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: MME were set to 26991897; 27588448

14 Dec 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MME were changed from Charcot-Marie-Tooth disease, axonal, type 2T, 617017 to Charcot-Marie-Tooth disease, axonal, type 2T, OMIM:617017

14 Dec 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q4_21_NHS_review tag was added to gene: MME.

5 Dec 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: MME was added gene: MME was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Other,Expert Review Green Mode of inheritance for gene: MME was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MME were set to 26991897; 27588448 Phenotypes for gene: MME were set to Charcot-Marie-Tooth disease, axonal, type 2T, 617017