Abstract: Objective: To identify the pathogenic genes in two cases of autosomal recessive woolly hair with hypotrichosis (ARWH/HT). Methods: Blood samples were collected from two Chinese Han families with ARWH/HT. Next-generation genodermatosis-targeted sequencing was employed to detect gene mutations in the DNA extracted from the blood samples. Sanger sequencing was then performed for family validation, and Minigene validation was utilized to assess the pathogenicity of splicing mutations. Results: The compound heterozygous mutations of c.742C>A (p.His248Asn) and c.982+12A>G  of LIPH gene were found in proband 1, and c.629-1_629delinsTT and c.686delAinsGTAGAACCCAACCTGGCT were found in proband 2. Sanger sequencing confirmed that these compound heterozygous mutations were inherited from their mother and father, respectively. The splicing mutations c.982+12A>G and c.629-1_629delinsTT, previously unreported, were functionally characterized through Minigene validation. Conclusion: We report two novel splicing mutations in the LIPH gene and demonstrate their pathogenicity through family and Minigene validation, thereby enriching the mutation spectrum associated with ARWH/HT.

Key words: ARWH/HT, LIPH gene, splicing mutation