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Although the patients had features of <jats:italic>MED27<\/jats:italic>\u2010related disorder, the <jats:italic>SLC6A7<\/jats:italic> and <jats:italic>MPPE1<\/jats:italic> variants were functionally investigated. <jats:italic>SLC6A7<\/jats:italic> variant <jats:italic>in vitro<\/jats:italic> overexpression caused decreased proline transport as a result of reduced cell\u2010surface expression, and zebrafish knockdown of <jats:italic>slc6a7<\/jats:italic> exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L\u2010proline transporter\u2013G396S RNA. Lastly, patient fibroblasts displayed reduced cell\u2010surface expression of glycophosphatidylinositol\u2010anchored proteins linked to <jats:italic>MPPE1<\/jats:italic> dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a family harboring a homozygous <jats:italic>MED27<\/jats:italic> variant with additional loss\u2010of\u2010function <jats:italic>SLC6A7<\/jats:italic> and <jats:italic>MPPE1<\/jats:italic> gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29147","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T08:22:14Z","timestamp":1658737334000},"page":"2139-2146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<i>MED27<\/i>, <i>SLC6A7,<\/i> and <i>MPPE1<\/i> Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-3105","authenticated-orcid":false,"given":"Kimberley M.","family":"Reid","sequence":"first","affiliation":[{"name":"Molecular Neurosciences, Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children UCL Great Ormond Street Institute of Child Health  London United 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