Abstract Details

Title Novel MME mutation (N689K) in an Argentine case with Charcot-Marie-Tooth and family history of pes cavus

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 080

Objective

This work provides further evidence about the pathogenicity of the novel MME N689K mutation.

Background Mutations in MME are associated with pes cavus phenotype and middle/late-onset Charcot-Marie-Tooth disease type 2T (CMT2T), with possible incomplete penetrance. Variants in this gene had also been associated with sporadic Alzheimer’s disease risk. Here we describe the finding of a novel MME c.2067C>A variant in an Argentine patient, who developed slowly progressive motor symptoms and difficulty to walk at the age of 40 and has a family history of pes cavus phenotype.

Design/Methods

The patient underwent clinical and neurophysiological evaluations including electromyogram and CSF analysis. Whole exome sequencing and Sanger validation were performed on the proband’s genomic DNA obtained from a blood sample. Co-segregation study was performed in the only available family member that has reached the age of onset for the disease.

Results Neurophysiological study of upper and lower limbs showed findings compatible with primarily axonal, sensory-motor polyneuropathy, with a predominance of lower limbs; CSF protein determination was normal, with negative oligoclonal bands. Exome sequencing revealed a novel heterozygous missense Asparagine-to-Lysine mutation at codon 689 of MME (NM_000902.3, c.2067C>A, Exon 21). This variant is classified as likely pathogenic according to ACMG guidelines and predicted to be damaging by CADD score and Polyphen-2, but hasn’t been described in any patients so far. Co-segregation test in proband’s sister (68-years-old) –who has pes cavus phenotype but no other symptoms- revealed that she’s also a mutation carrier. Taken together, these results and proband’s family medical history support the role of the variant in the disease pathogenesis.

Conclusions We report a novel heterozygous MME N689K mutation in a patient with CMT2T, with familial pes cavus phenotype. Taken together with previous reports of other mutations in this gene, our data strongly suggest that this variant is likely pathogenic, with variable expressivity.

Authors/Disclosures
Micaela Kennedy, MSc (Fleni) PRESENTER	Miss Kennedy has nothing to disclose.
Lucas Alessandro, Sr., MD (FLENI)	Dr. Alessandro has nothing to disclose.
Martin Genco	MARTIN RAGGIO has nothing to disclose.
	No disclosure on file
	No disclosure on file

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Abstract Details