Prevalent founder mutation c.736T>A of LIPH in autosomal recessive woolly hair of Japanese leads to variable severity of hypotrichosis in adulthood

Background Mutations in LIPH are a cause of autosomal recessive woolly hair (ARWH). Homozygous c.736T>A (p.Cys246Ser), and compound heterozygous c.736T>A and c.742C>A (p.His248Asn) have been reported in 5 and 7 Japanese children with ARWH respectively. The severity of hypotrichosis is known to be able to change in the clinical course, and the mutation patterns of LIPH do not always correlate with the severity of hypotrichosis in ARWH caused by other mutation sites of LIPH. However, all 12 Japanese children previously reported to have ARWH have shown similar severity of hypotrichosis. Objective In this study, we investigated the clinical features and molecular basis of ARWH in patients including three adults (three adults and two children) from five non-related Japanese families. Methods Five families of Japanese origin that presented with woolly hair were studied. The phenotype was confirmed by clinical examination. Direct automated DNA sequencing of the LIPH gene was performed to identify the mutations in our probands. Results All patients had had woolly hair since birth. Homozygous c.736T>A mutations were found in four patients, including three adult cases, and compound heterozygous c.736T>A and c.742C>A mutations were found in one child patient. The two adults and two children had only sparse scalp hair, although one adult woman had mild hypotrichosis with long hairs. Conclusion Some patients with homozygous c.736T>A can have a mild hypotrichosis phenotype with long hairs in adulthood.