Compound Heterozygous Mutations in the Hairless Gene in Atrichia with Papular Lesions

Paller, Amy S.; Varigos, George; Metzker, Arye; Bauer, Robert C.; Opie, Jacinta; Martı́nez-Mir, Amalia; Christiano, Angela M.; Zlotogorski, Abraham

doi:10.1046/j.1523-1747.2003.12370.x

Cited by 21 publications

(18 citation statements)

References 14 publications

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“…Based on current mutations, the correlations between type and location of HR mutations and phenotype are difficult to establish. Hypopigmented streaks have been described in two Arab, two Moroccan, one Australian, one Caucasian and one Korean families [2,19,20,21,22,23,24], which shows that atrichia patients share whitish streaks not particular to Arab origin, first described in 2002 [2]. The hallmark manifestation has occurred in Australoid, Xanthochroic and Mongoloid, which favors the universality of this abnormality.…”

Section: Discussionmentioning

confidence: 95%

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

Wang

Tu²,

Feng³

et al. 2013

Dermatology

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Background: Congenital atrichia with papular lesions (APL) is characterized by complete absence of body hair shortly after birth, along with papules, and caused by mutations in the hairless gene (HR). Objective: To investigate whether APL with HR mutations might also be found among patients in non-consanguineous Chinese families and to discuss the phenotypic variations with the same mutations. Methods: DNA sequencing of the HR was performed in the Chinese pedigree and in 100 controls. Results: A nonsense mutation c.T2265A in the patient and his father as well as a 2bp deletion (3482delCT) in the patient and his mother were detected. Conclusion: Our study identified the first mutation in exon 10 in HR as well as the second novel compound heterozygous mutations in a Chinese family, also adding new variants to the knowledge of HR mutations in APL. Phenotypic heterogeneity in congenital atrichia might be subject to the founder genes or modifier genes.

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Section: Discussionmentioning

confidence: 95%

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

Wang

Tu²,

Feng³

et al. 2013

Dermatology

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“…Most reported cases of APL have been discovered in consanguineous families living within a restricted geographical region. However, there are some reports of APL patients with compound heterozygous mutations in small non-consanguineous families [7][8][9][10][11] . In present study, the novel missense mutation was not inherited as an autosomal recessive, as the patient's mother and maternal grandfather were heterozygous carriers of the G64E mutation, whereas his father had the wild-type HR gene.…”

Section: Discussionmentioning

confidence: 99%

“…Most APL patients have homozygous HR gene mutations, and have been discovered in consanguineous families living within a restricted geographical region, implying that these mutations became fixed owing to a high degree of consanguinity [1][2][3] . However, the number of sporadic cases occurring in offspring of unrelated parents has been increasing [7][8][9][10][11] . Sporadic patients with non-consanguineous parents have been misdiagnosed with alopecia universalis (AU) frequently, as APL and AU are clinically very similar.…”

Section: Introductionmentioning

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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Compound Heterozygous Mutations in the Hairless Gene in Atrichia with Papular Lesions

Cited by 21 publications

References 14 publications

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

Atrichia with Papular Lesions in a Chinese Family Caused by Novel Compound Heterozygous Mutations and Literature Review

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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