Complete defect in PA-PLA1α secretion function leading to autosomal recessive woolly hair and hypotrichosis: insights from a novel compound heterozygous LIPH variant study in a Chinese pedigree

We identified a novel missense variant (NM_139248.3: c.530T>G: p.Leu177Arg) and a previously reported missense variant (c.742C>A: p.His248Asn) of LIPH in the patient. TA cloning demonstrated that these variants were located on different alleles, supporting an autosomal recessive inheritance pattern. In silico tools predicted the novel variant to be disease-causing, likely reducing the stability of PA-PLA1α, the protein encoded by LIPH. PA-PLA1α, a member of the AB hydrolase superfamily and the lipase family, functions as a secreted protein to perform its hydrolytic and catalytic activities. Through a secretion assay, we observed that the novel missense variant c.530T>G almost abolished the secretion of the variant protein compared to the control (p<0.0001).