ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser63 amino acid residue in MPZ. Other variant that disrupt this residue have been observed in affected individuals (PMID: 22734905, 7693130, 12402337, 8835320), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Experimental studies using transgenic mouse models have shown that this missense change [p.Ser63Cys] creates a packing defect in the myelin sheath that leads to hypomyelination and these mice develop tremor, ataxia, weakness and muscle atrophy of hind limbs recapitulating phenotypes observed in human neuromuscular disease (PMID: 16495463, 20937820). This variant has been observed to be de novo in an individual affected with Dejerine-Sottas syndrome (PMID: 7506095). ClinVar contains an entry for this variant (Variation ID: 14169). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with cysteine at codon 63 of the MPZ protein (p.Ser63Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine.