Analysis of unique mutations in the LPAR6 gene identified in a Japanese family with autosomal recessive woolly hair/hypotrichosis: Establishment of a useful assay system for LPA(6)

作者：Hayashi Ryota; Inoue Asuka; Suga Yasushi; Aoki Junken; Shimomura Yutaka^*

来源：Journal of Dermatological Science, 2015, 78(3): 197-205.

DOI：10.1016/j.jdermsci.2015.03.006

• Woolly hair
• Hypotrichosis
• LPAR6
• LPA(6)
• LIPH

Background: Woolly hair (WH) is a hair shaft anomaly characterized by tightly-curled hair and is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal dominant or recessive inheritance. The autosomal recessive form of WH (ARWH) is caused by mutations in either lipase H (LIPH) or lysophosphatidic acid receptor 6 (LPAR6) gene, encoding an LPA-producing enzyme PA-PLA(1)alpha and an LPA receptor LPA(6), respectively.
Objective: To define the molecular basis of ARWH/hypotrichosis in a Japanese family.
Methods: We performed mutational analysis of candidate genes and a series of expression and in vitro functional analyses, which we improved in this study, to determine the consequences resulting from the mutations identified in the family.
Results: Novel compound heterozygous LPAR6 mutations were identified in the patient. One was a nonsense mutation c.756T > A (p.Tyr252*); the other was a large insertion mutation within the promoter region of LPAR6. Expression studies detected LPAR6 mRNA only from the c.756T > A allele in the patient's hair follicles, suggesting that the insertion in the other allele disrupted the LPAR6 promoter and thus led to a failure of transcription. Furthermore, an improved LPA(6) functional assay developed in this study demonstrated aberrant expression and a subsequent loss of function of the p.Tyr252*-mutant protein.
Conclusion: Through establishing a useful assay system for LPA(6), our results further underscore the crucial roles of LPAR6 in hair follicle development and hair growth in humans at molecular levels.

• 出版日期2015-6