Marie Unna hereditary hypotrichosis: Identification of a U2HR mutation in the family from the original 1925 report

Background In 1925, Dr Marie Unna described a rare form of hereditary hypotrichosis in a German multigenerational family. This was later termed "Marie Unna hereditary hypotrichosis" (MUHH). MUHH is an autosomal dominant disorder that is characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth; coarse and wiry hair during childhood; and progressive hair loss beginning around puberty. Causal mutations in U2HR , an inhibitory upstream open reading frame in the 5'-untranslated region of the human hairless ( HR ) gene, were recently identified in several unrelated MUHH families from various ethnic backgrounds. Objective Although there have been several clinical reports of descendants of the originally described family, the molecular cause of disease in this particular family has not been established. The aim of this study was to investigate descendants of this family and to analyze their DNA for the presence of U2HR mutations. Methods Descendants of the family (including one affected individual) were examined clinically. Direct sequencing of U2HR was performed. Enzymatic digestion using the restriction enzyme Nco I was performed to confirm the sequencing results. Results The index patient displayed the typical MUHH pattern of hair loss and was found to carry the disease-causing c.3G>A (p.M1I) U2HR mutation. This mutation was not detected in unaffected family members. Limitations Only one affected family member was investigated. Conclusions Eighty-five years after the first description of this rare form of alopecia, the disease-causing mutation in the originally reported family has been identified.