Novel Hairless Mutations in Two Kindreds with Autosomal Recessive Papular Atrichia

Kruse, Roland; Cichon, Sven; Anker, M.; Hillmer, Axel M.; Barros‐Núñez, Patricio; Cantú, J. M.; Leal, Evelia; Weinlich, Georg; Schmuth, Matthias; Fritsch, Peter; Ruzicka, Thomas; Propping, Peter; Nöthen, Markus M.

doi:10.1046/j.1523-1747.1999.00790.x

Cited by 62 publications

(52 citation statements)

References 18 publications

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“…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.…”

Section: Hr Function In Vivomentioning

confidence: 99%

“…The original mutation was caused by insertion of an endogenous retrovirus, and the murine hr gene was cloned by mapping the retroviral insertion site (Stoye et al 1988;Cachon-Gonzalez et al 1994). The human ortholog was subsequently found to be associated with congenital hair disorders (alopecia universalis and papular atrichia; Ahmad et al 1998Ahmad et al , 1999Cichon et al 1998;Kruse et al 1999;Sprecher et al 1999). Multiple murine and human alleles have been characterized, and all share a distinctive phenotype in which initial hair growth is normal, but after shedding, the hair does not regrow (Lyon and Searle 1989;Panteleyev et al 1998;Ahmad et al 1999).…”

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confidence: 99%

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

Potter¹,

Beaudoin²,

DeRenzo³

et al. 2001

Genes Dev.

167

179

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The mammalian hairless (hr) gene plays a critical role in the maintenance of hair growth. Although the hr gene has been identified, the biochemical function of its encoded protein (Hr) has remained obscure. Here, we show that Hr functions as a transcriptional corepressor for thyroid hormone receptors (TRs). We find that two independent regions of Hr mediate TR binding and that interaction requires a cluster of hydrophobic residues similar to the binding motifs proposed for nuclear receptor corepressors (N-CoR and SMRT). Similarly, we show that Hr binds to the same region of TR as known corepressors. We show that Hr interacts with histone deacetylases (HDACs) and is localized to matrix-associated deacetylase (MAD) bodies, indicating that the mechanism of Hr-mediated repression is likely through associated HDAC activity. Thus, Hr is a component of the corepressor machinery, and despite its lack of sequence identity with previously described corepressors, its mode of action is remarkably conserved. On the basis of its thyroid hormone-inducible and tissue-and developmental-specific expression, Hr likely defines a new class of nuclear receptor corepressors that serve a more specialized role than ubiquitous corepressors. The discovery that Hr is a corepressor provides a molecular basis for specific hair loss syndromes in both humans and mice.

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Section: Hr Function In Vivomentioning

confidence: 99%

mentioning

confidence: 99%

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

Potter¹,

Beaudoin²,

DeRenzo³

et al. 2001

Genes Dev.

167

179

View full text Add to dashboard Cite

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“…Approximately 34 mutations of the HR gene, including the one discovered in this study, have been reported 6,[10][11][12][20][21][22] . These include missense, nonsense, deletion, insertion, splice-site, and compound heterozygous mutations 10,11,[23][24][25] .…”

Section: Discussionmentioning

confidence: 99%

Detection of a Novel Missense Mutations in Atrichia with Papular Lesions

et al. 2011

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Background: Atrichia with papular lesions (APL) is a rare inherited disease characterized by early onset of total hair loss, followed by papular lesions over the extensor areas of the body. Recently, mutations in the human hairless (HR) gene have been implicated in its pathogenesis. The identification of mutations in the HR gene is important for differentiating between APL and alopecia universalis (AU). Objective: We compared the HR genes of patients with presumed AU who showed minimal or no response to treatment with the HR genes of healthy controls. Methods: The subjects were 11 patients with presumed AU who had not responded to treatments. Fifty healthy people were included as controls for molecular analysis. To screen for mutations, polymerase chain reaction was performed. Results: DNA analysis identified a novel heterozygous G-to-A transition at nucleotide position 191 in exon 5. The mutation was not found in the controls, other AU patients, or any unaffected family members except for the patients' mother and maternal grandfather, who were heterozygous HR gene carriers. Conclusion: Our study identifies a novel missense mutation in exon 5 of the HR gene in a Korean APL patient previously diagnosed as AU.

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“…This form of hair loss is irreversible and histology is consistent with an absence of mature hair follicles. APL was mapped to chromosome 8p12 and mutations in the Hairless (HR) gene have been found in a growing number of APL patients [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. The diagnosis of APL requires detailed family history, especially of consanguinity, a clinical history, DNA sampling, and identification of a HR mutation.…”

Section: Introductionmentioning

confidence: 99%

“…The diagnosis of APL requires detailed family history, especially of consanguinity, a clinical history, DNA sampling, and identification of a HR mutation. Using these methods, we and others have identified several types of pathogenic HR mutations in multiple families of various ethnic backgrounds including nonsense, missense, insertion and deletion mutations [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin

Kim

Wajid

Kraemer

et al. 2007

Journal of Dermatological Science

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Abstract(1) Background-Atrichia with papular lesions (APL) is a rare autosomal recessive form of inherited alopecia. Affected individuals present with a distinct pattern of total hair loss on the scalp, axilla and body shortly after birth and are essentially devoid of eyelashes and eyebrows. This form of hair loss is irreversible and the histology is consistent with an absence of mature hair follicles. In addition to total atrichia, APL patients also present with papules and follicular cysts filled with cornified material. Mutations in the Hairless (HR) gene have been shown to underlie APL.(2) Objective-Here, we studied five unrelated large Pakistani families with clinical manifestations of APL.(3) Methods-Based on previous reports of HR mutations in APL, we performed direct DNA sequencing analysis.(4) Results-DNA sequencing of the HR gene in APL patients revealed three novel nonsense mutations in five unrelated families. All affected individuals were homozygous for a nonsense mutation due to C-to-T transitions at different positions in the amino acid sequence. Two families carry the mutation Q323X (CAG-TAG) in exon 3, two families harbor the mutation Q502X (CAG-TAG) in exon 6, and one family had a mutation at R940X (CGA-TGA) in exon 14. Haplotype analysis revealed that all affected individuals of both APL1 and APL16 families were homozygous for the same haplotype, and likewise, the mutation in families APL2 and APL19 was on the the same haplotype.(5) Conclusions-We report three novel nonsense mutations in the HR gene in APL. Two of the newly identified mutations, Q323X and Q502X, were found to be shared between unrelated families and marker analysis confirmed an identical homozygous haplotype for APL1 and APL16, and for APL2 and APL19. These findings suggest that Q323X and Q502X did not arise independently, but instead appear to have been propagated in the population. Collectively, these findings contribute further evidence for the involvement of hairless mutations in papular atrichia.

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Novel Hairless Mutations in Two Kindreds with Autosomal Recessive Papular Atrichia

Cited by 62 publications

References 18 publications

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

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

Detection of a Novel Missense Mutations in Atrichia with Papular Lesions

Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin

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