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Med."],"abstract":"<jats:p>Melanophilin (MLPH) functions as a linker between RAB27A and myosin Va (MYO5A) in regulating skin pigmentation during the melanosome transport process. The MYO5A-MLPH-RAB27A ternary protein complex is required for anchoring mature melanosomes in the peripheral actin filaments of melanocytes for subsequent transfer to adjacent keratinocytes. Griscelli syndrome type 3 (GS3) is caused by mutations in the <jats:italic>MLPH<\/jats:italic> gene. So far, only five variants of <jats:italic>MLPH<\/jats:italic> associated with GS3 have been reported. Here, we reported the first patient with GS3 in a Chinese population. The proband carried a novel homozygous missense mutation (c.73G&amp;gt;C; p.D25H), residing in the conserved Slp homology domain of MLPH, and presented with hypopigmentation of the hair, eyebrows, and eyelashes. Light microscopy revealed the presence of abnormal pigment clumping in his hair shaft. <jats:italic>In silico<\/jats:italic> tools predicted this <jats:italic>MLPH<\/jats:italic> variant to be likely pathogenic. Using immunoblotting and immunofluorescence analysis, we demonstrated that the MLPH (D25H) variant had an inhibitory effect on melanosome transport by exhibiting perinuclear melanosome aggregation in melanocytes, and greatly reduced its binding to RAB27A, although the protein level of MLPH in the patient was not changed. Our findings suggest that MLPH (D25H) is a pathogenic variant that expands the genetic spectrum of the <jats:italic>MLPH<\/jats:italic> gene.<\/jats:p>","DOI":"10.3389\/fmed.2022.896943","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T07:35:30Z","timestamp":1651822530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient"],"prefix":"10.3389","volume":"9","author":[{"given":"Qiaorong","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yefeng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanjuan","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianjiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiumin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1093\/icb\/icab078","article-title":"Melanosome biogenesis in the pigmentation of mammalian skin","volume":"61","author":"Le","year":"2021","journal-title":"Integr Comp Biol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.13030","article-title":"New insights into the pathogenesis of hermansky-pudlak syndrome","author":"Li","year":"2022","journal-title":"Pigment Cell Melanoma Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1042\/BST0391191","article-title":"Melanosomes on the move: a model to understand organelle dynamics","volume":"39","author":"Hume","year":"2011","journal-title":"Biochem Soc Trans."},{"key":"B4","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/pcmr.12931","article-title":"Rab GTPases: Key players in melanosome biogenesis, transport, and transfer","volume":"34","author":"Fukuda","year":"2021","journal-title":"Pigment Cell Melanoma Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25423","DOI":"10.1074\/jbc.M202574200","article-title":"A family of Rab27-binding proteins. 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