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Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient
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 subs...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120966/ https://www.ncbi.nlm.nih.gov/pubmed/35602484 http://dx.doi.org/10.3389/fmed.2022.896943 |
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author | Huang, Qiaorong Yuan, Yefeng Gong, Juanjuan Zhang, Tianjiao Qi, Zhan Yang, Xiumin Li, Wei Wei, Aihua |
author_facet | Huang, Qiaorong Yuan, Yefeng Gong, Juanjuan Zhang, Tianjiao Qi, Zhan Yang, Xiumin Li, Wei Wei, Aihua |
author_sort | Huang, Qiaorong |
collection | PubMed |
description | 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 MLPH gene. So far, only five variants of MLPH 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>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. In silico tools predicted this MLPH 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 MLPH gene. |
format | Online Article Text |
id | pubmed-9120966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91209662022-05-21 Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient Huang, Qiaorong Yuan, Yefeng Gong, Juanjuan Zhang, Tianjiao Qi, Zhan Yang, Xiumin Li, Wei Wei, Aihua Front Med (Lausanne) Medicine 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 MLPH gene. So far, only five variants of MLPH 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>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. In silico tools predicted this MLPH 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 MLPH gene. Frontiers Media S.A. 2022-05-06 /pmc/articles/PMC9120966/ /pubmed/35602484 http://dx.doi.org/10.3389/fmed.2022.896943 Text en Copyright © 2022 Huang, Yuan, Gong, Zhang, Qi, Yang, Li and Wei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Huang, Qiaorong Yuan, Yefeng Gong, Juanjuan Zhang, Tianjiao Qi, Zhan Yang, Xiumin Li, Wei Wei, Aihua Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title | Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title_full | Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title_fullStr | Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title_full_unstemmed | Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title_short | Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient |
title_sort | identification of a novel mlph missense mutation in a chinese griscelli syndrome 3 patient |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120966/ https://www.ncbi.nlm.nih.gov/pubmed/35602484 http://dx.doi.org/10.3389/fmed.2022.896943 |
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