A novel missense mutation (C622G) in the zinc‐finger domain of the human hairless gene associated with congenital atrichia with papular lesions

Abstract

Congenital atrichia with papular lesions is a rare, recessively inherited form of hair loss characterized by a complete absence of all body hair shortly after birth. Mutations in the human ortholog of the mouse hairless (hr) gene have been implicated in the pathogenesis of this disorder. In this study, we screened, by direct sequence analysis, the hairless gene in a family of Polish descent and identified a novel missense mutation (C622G). The mutation alters the third of four invariant cysteins in the zinc-finger domain, which has high homology to the C-X-X-C-(X)17-C-X-X-C structure of the zinc-fingers of the GATA family of transcription factors. The human hairless gene encodes a putative transcription factor with restricted expression in the brain and skin, which is involved in the regulation of apoptosis during catagen remodeling in the hair cycle.

Characterization of a Nitric Oxide Synthase from the Plant Kingdom: NO Generation from the Green Alga Ostreococcus tauri Is Light Irradiance and Growth Phase Dependent

“…A C-(x) 3 -C motif has thus far only been described in NOS proteins from O. tauri and O. lucimarinus. However, the zinc finger domain present in the GATA family of transcription factors is C-(x) 2 -C (Aita et al, 2000), and the zinc finger domain of the cytochrome oxidase has a highly conserved C-(x) 3 -C motif (Jaksch et al, 2001), indicating that the C-(x) 3 -C motif present in O. tauri NOS could bind zinc. Moreover, the amino acids P and R are present within (x) 3 , between the two C residues in the putative zinc binding domains [C-(x) 3 -C] of NOS from Ostreococcus species and are conserved among most eNOS proteins described to date.…”

The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor

“…The biological function of Hr can be inferred from the phenotype of humans and mice with mutations in the hr gene. Mutation of the human hr gene results in congenital hair loss disorders (papular atrichia and alopecia universalis) and, in some cases, associated neurological deficits (del Castillo et al 1974;Ahmad et al 1998Ahmad et al , 1999Cichon et al 1998;Kruse et al 1999;Sprecher et al 1999;Aita et al 2000). Thus, these disorders are an example of human disease resulting from aberrant corepressor function.…”

“…Consistent with this idea, phenotypic analysis of hr mutant (the hr rh allele) mice has revealed alterations in neuronal morphology and inner ear defects (Lyon and Searle 1989;Garcia-Atares et al 1998;Cachon-Gonzalez et al 1999). In humans, neurological deficits are sometimes correlated with the hair loss phenotype of hr mutants, as there are multiple cases in which concurrent mental retardation is observed (del Castillo et al 1974;Aita et al 2000).…”

Dermatopathology and molecular genetics

“…Both APL and AUC have been shown to be caused by underlying mutations in the human hairless gene. [30][31][32][33][34][35][36][37][38][39][40] It has been noted that the alopecia associated with vitamin Dedependent rickets type II, which results from mutations in the vitamin-D receptor (VDR), and the alopecias associated with mutations in the hairless gene (APL and AUC) have similar clinical and histologic features. 41,42 The histologic characteristics of the alopecias associated with vitamin Dedependent rickets type II, APL, and AUC were recently studied in a systematic and comparative fashion.…”