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A case of a childhood onset developmental encephalopathy with a novel de novo truncating variant in the Membrane Protein Palmitoylated 5 (MPP5) gene

Published:January 23, 2023DOI:https://doi.org/10.1016/j.seizure.2023.01.015

      Abstract

      Background

      Membrane Protein Palmitoylated 5 (MPP5) is a highly conserved apical complex protein, essential for cell polarity. Defects in neuronal cell polarity are associated with neurologic disorders. Only three patients with heterozygous MPP5 de novo variants have been reported so far, with global developmental delay, behavioral changes and in only one case epileptic seizures.

      Objective

      To describe a new patient with a novel truncating de novo mutation in MPP5 and to characterize in detail the epileptic phenotype and electroencephalographic features of the encephalopathy.

      Methods

      We identified a novel truncating de novo mutation in MPP5 in a 44 year old patient by exome sequencing (p.Ser498Phefs*15). We retrospectively analyzed his clinical and instrumental data along a thirty-year follow up.

      Result

      Our patient presents with generalized tonic-clonic seizures, myoclonic and clonic seizures, non-epileptic myoclonus, tremor, severe intellectual disability, mild face dysmorphic traits, and psychosis.

      Discussion and conclusion

      We present a case of a childhood onset developmental encephalopathy with a likely-pathogenic variant in the MPP5 gene.. This represents the first complete description of the epileptic syndrome associated with the MPP5 gene.

      Keywords

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      References

        • Hakanen J.
        • Ruiz-Reig N.
        • Tissir F.
        Linking cell polarity to cortical development and malformations.
        Front Cell Neurosci. 2019; 13 (Jun 4PMID: 31213986; PMCID: PMC6558068): 244https://doi.org/10.3389/fncel.2019.00244
        • Sterling N.
        • Duncan A.R.
        • Park R.
        • Koolen D.A.
        • Shi J.
        • Cho S.H.
        • Benke P.J.
        • Grant P.E.
        • Genetti C.A.
        • VanNoy G.E.
        • Juusola J.
        • McWalter K.
        • Parboosingh J.S.
        • Lamont R.E.
        • Bernier F.P.
        • Smith C.
        • Harris D.J.
        • Stegmann A.P.A.
        • Innes A.M.
        • Kim S.
        • Agrawal P.B.
        De novo variants in MPP5 cause global developmental delay and behavioral changes.
        Hum Mol Genet. 2020; 29 (Dec 18PMID: 33073849; PMCID: PMC7906781): 3388-3401https://doi.org/10.1093/hmg/ddaa224
        • Hurd T.W.
        • Gao L.
        • Roh M.H.
        • Macara I.G.
        • Margolis B.
        Direct interaction of two polarity complexes implicated in epithelial tight junction assembly.
        Nat Cell Biol. 2003; 5 (FebPMID: 12545177): 137-142https://doi.org/10.1038/ncb923
        • Kamberov E.
        • Makarova O.
        • Roh M.
        • Liu A.
        • Karnak D.
        • Straight S.
        • Margolis B.
        Molecular cloning and characterization of Pals, proteins associated with mLin-7.
        J Biol Chem. 2000; 275 (Apr 14PMID: 10753959Roh et al. 2002): 11425-11431https://doi.org/10.1074/jbc.275.15.11425
        • Roh M.H.
        • Liu C.J.
        • Laurinec S.
        • Margolis B.
        The carboxyl terminus of zona occludens-3 binds and recruits a mammalian homologue of discs lost to tight junctions.
        J Biol Chem. 2002; 277 (Jul 26Epub 2002 May 20. PMID: 12021270): 27501-27509https://doi.org/10.1074/jbc.M201177200
        • Makarova O.
        • Roh M.H.
        • Liu C.J.
        • Laurinec S.
        • Margolis B.
        Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1).
        Gene. 2003; 302 (Jan 2PMID: 12527193): 21-29https://doi.org/10.1016/s0378111902010843
        • Scheffer I.E.
        • et al.
        ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology.
        Epilepsia. 2017; 58 (April): 512-521https://doi.org/10.1111/epi.13709