Analysis of hair disorders caused by mutations in lipid-related genes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Shimomura Yutaka 山口大学, 大学院医学系研究科, 教授 (70397107)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脂質関連遺伝子 / LSS / 乏毛症 / PLCD1

Outline of Final Research Achievements

In this study, we performed detailed expression and functional studies in cultured cells in order to disclose genotype-phenotype correlations for LSS gene mutations, which have been reported to underlie several distinct diseases. We overexpressed wild-type and a total of 6 LSS gene mutants (G12D, R177Q, V487E, P549L, W581R, T705K) in cultured cells and analyzed their expression patterns and the ability to generate lanosterol. However, we did not find obvious differences in either expression or function between the LSS gene mutations analyzed. Nevertheless, we were able to further characterize the hair shaft anomalies resulting from LSS gene mutations. In addition, we reconfirmed that mutations in SREBF1 and PLCD1 genes underlie a congenital hair disorder and a familial hair follicle-derived tumor, respectively. Our data further highlight that lipid-related genes are involved in causing various hair disorders in humans.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、LSS遺伝子変異に関するgenotype-phenotype correlationを明確にする知見を得ることはできなかったが、同遺伝子変異による毛髪異常の特徴はかなり明らかになり、診断を決定する際の一助になると思われる。また、SREBF1, PLCD1はともに脂質関連遺伝子であり、それらの異常が先天性毛髪疾患や毛包系腫瘍の発症に関与していることが改めて示された。特に、PLCD1遺伝子におけるmonoallelic two hitsという現象は腫瘍の発生過程としては極めてまれな現象である。本研究は、脂質関連遺伝子の毛包における役割や重要性を解き明かす足がかりになったと思われる。