AUTHOR=Huang Qiaorong , Yuan Yefeng , Gong Juanjuan , Zhang Tianjiao , Qi Zhan , Yang Xiumin , Li Wei , Wei Aihua 

TITLE=Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.896943

DOI=10.3389/fmed.2022.896943

ISSN=2296-858X

ABSTRACT=Melanophilin (MLPH) functions as a linker between RAB27A and myosin Va (MYO5A) in regulating skin pigmentation in the melanosome transport process. The RAB27A-MLPH- MYO5A 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. There are only five variants of MLPH associated with GS3 that have been reported so far. Here, we reported the first GS3 patient 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 hypomelanosis 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 pathogenic. Using immunoblotting and immunofluorescence analysis, we demonstrated 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 which expands the genetic spectrum of MLPH gene.