Hereditary neuropathy

Gene: MME

Comment on mode of inheritance: Updating from 'biallelic' to 'both mono- and biallelic' inline with MOI on equivalent GMS panel (R78 Hereditary neuropathy or pain disorder v3.24).

"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"

Created: 24 Jan 2024, 11:03 a.m. | Last Modified: 24 Jan 2024, 11:11 a.m.

Panel Version: 1.476

Green List (high evidence)

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.

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.

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.

Green List (high evidence)

Further patient identified through 100,000 Genomes Cohort

Created: 19 Jan 2017, 10:52 a.m.

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

• PubMed: 26991897