Abstract Congenital atrichia is a rare autosomal recessive disorder of hair development, characterized by complete loss of hair shortly after birth. Evidence of linkage to chro­mosome 8p12 has been established, implicating the human homolog of the mouse hairless (hr) gene as a candidate gene. We have previously identified missense mutations in families with congenital atrichia. Here, we report the first deletion mutation (2147del C) in exon 9 of the human hair­less gene leading to a frameshift and downstream prema­ture termination codon in five Palestinian families of Arab origin.

The formation of a hair follicle involves a complex series of reciprocal interactions between the dermis and epidermis, resulting in the formation of an epidermal placode and hair plug, a dermal papilla, and finally, the differentiation of epi­dermal cells to form the inner root sheath and hair shaft of the follicle (Hardy 1992). The initial message is derived from the dermis and instructs the overlying epidermis to thicken, forming a placode and then a downgrowth into the dermis, known as the hair plug. An epidermal message passes from the hair plug to the dermis, resulting in the con

densation of a cluster of mesenchymal cells that will even­tually form the dermal papilla. The dermal papilla then stimulates the division of overlying, epithelially derived matrix cells in the hair plug. These cells divide rapidly and differentiate into either inner root sheath cells or hair shaft cells, depending on their position in relation to the longitu­dinal axis of the follicle . Hair growth pro­ceeds in a cyclical fashion throughout life, with the growth phase being followed by a regression phase (during which the upper portion of the follicle degenerates) and a resting phase. At the end of the resting phase, epidermal stem cells located in the bulge region of the outer root sheath are thought to be recruited by signals from the dermal papilla to form the hair matrix, and a new cycle of growth is initiated . Although these events have been described extensively in model systems, the genes governing these processes are largely unknown.

There are many forms of inherited alopecia or hair loss, showing extensive variation in age of onset, severity, and associated ectodermal abnormalities. Congenital alopecia universalis (MIM 203655) or congenital atrichia (MIM 209500) without associated ectodermal defects is very rare and is inherited as an autosomal recessive trait. We and oth­ers have recently reported a linkage of this form of atrichia to chromosome 8p12 . Further, we have mapped the human homolog of the hairless gene in the same region of chromosome 8 and have identified pathogenetic mutations in this form of atrichia . The hairless gene product is a pu­tative transcription factor with a single zinc-finger domain and is highly expressed in the brain and the skin. It appears to function in the cellular transition to the first adult hair cy­cle, and in its absence, hair growth completely ceases, a new hair is never induced, and the result is a complete form of inherited alopecia.