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Biallelic predicted truncating <jats:italic>P4HTM<\/jats:italic> variants were identified following trio whole-genome sequencing, consistent with a diagnosis of hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy and eye abnormalities (HIDEA) syndrome. Very few patients with HIDEA syndrome have been reported previously and mitochondrial abnormalities were observed in three of four previous cases who had a muscle biopsy, suggesting the possibility that HIDEA syndrome represents a primary mitochondrial disorder. <jats:italic>P4HTM<\/jats:italic> encodes a transmembrane prolyl 4-hydroxylase with putative targets including hypoxia inducible factors, RNA polymerase II and activating transcription factor 4, which has been implicated in the integrated stress response observed in cell and animal models of mitochondrial disease, and may explain the mitochondrial dysfunction observed in HIDEA syndrome.<\/jats:p>","DOI":"10.1038\/s41431-021-00932-8","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T04:02:39Z","timestamp":1626753759000},"page":"1536-1541","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biallelic P4HTM variants associated with HIDEA syndrome and mitochondrial respiratory chain complex I deficiency"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8599-8890","authenticated-orcid":false,"given":"Eleanor","family":"Hay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1200-2858","authenticated-orcid":false,"given":"Louise C.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethan","family":"Hoskins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-8335","authenticated-orcid":false,"given":"Martin","family":"Samuels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinki","family":"Munot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-730X","authenticated-orcid":false,"given":"Shamima","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"932_CR1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.clp.2015.02.008","volume":"42","author":"SE Sparks","year":"2015","unstructured":"Sparks SE. 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