Marie Unna hereditary hypotrichosis caused by a novel mutation in the human hairless transcript

Recently the causes for various forms of hypotrichosis and atrichia have been identified, increasing our understanding of the pathways involved in hair cycling and morphogenesis. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript were found as the cause for autosomal dominant Marie Unna hereditary hypotrichosis. At present, only two studies identified several pathogenic mutations. We ascertained a Jewish Ashkenazi family with hypotrichosis simplex of the Marie Unna type in a mother and her two children. Sequencing of the upstream ORF U2HR in the 5' UTR of the hairless gene resulted in the identification of a novel heterozygous missense mutation c.74C > T resulting in the amino acid change p.P25L. Functional assays confirmed that this mutation led to increased translation of the main HR ORF. This finding extends the mutations' spectrum of U2HR, and emphasizes its major role in hair growth.