机构：[1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China,首都医科大学附属北京同仁医院临床科室皮肤性病科[2]Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing, China,首都医科大学附属北京儿童医院[3]Rare Disease Center, National Center for Children’s Health, Beijing, China,[4]MOE Key Laboratory of Major Diseases in Children, Beijing, China,[5]Beijing Children’s Hospital, Capital Medical University, Beijing, China首都医科大学附属北京儿童医院
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.
基金：
This work was partially supported by grants from the Ministry
of Science and Technology of China [2019YFA0802104
(WL)] and from the National Natural Science Foundation
of China [(82173447 (AW), 31830054 (WL), and
31900496 (YY)].
第一作者机构：[1]Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China,
共同第一作者：
通讯作者：
通讯机构：[2]Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing, China,[3]Rare Disease Center, National Center for Children’s Health, Beijing, China,[4]MOE Key Laboratory of Major Diseases in Children, Beijing, China,[5]Beijing Children’s Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Huang Qiaorong,Yuan Yefeng,Gong Juanjuan,et al.Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient[J].FRONTIERS IN MEDICINE.2022,9:896943.doi:10.3389/fmed.2022.896943.
APA：
Huang, Qiaorong,Yuan, Yefeng,Gong, Juanjuan,Zhang, Tianjiao,Qi, Zhan...&Wei, Aihua.(2022).Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient.FRONTIERS IN MEDICINE,9,
MLA：
Huang, Qiaorong,et al."Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient".FRONTIERS IN MEDICINE 9.(2022):896943
