Ann Dermatol.  2011 May;23(2):132-137. 10.5021/ad.2011.23.2.132.

Detection of a Novel Missense Mutations in Atrichia with Papular Lesions

• Lee D
• Kim SH
• Chun JS
• Joo MH
• Kim JY
• Hwang SW
• Kang HJ
• Park SW
• Sung HS

• KMID: 2156652
• DOI: http://doi.org/10.5021/ad.2011.23.2.132

Abstract

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.

Keyword

Alopecia universalis; Atrichia with popular lesions; Hairless gene; Missense mutation

MeSH Terms

Alopecia
DNA
Exons
Hair
Hair Follicle
Humans
Mothers
Mutation, Missense
Polymerase Chain Reaction
Skin Diseases, Vesiculobullous
Alopecia
DNA
Hair Follicle
Skin Diseases, Vesiculobullous

Figure

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  Fig. 1 Clinical appearance of the APL patient. (A, B) There is complete loss of hair on the scalp, and the eyebrows and eyelashes are sparse. (A, C, D) There are follicular papules on the face, elbows, and knees. (E) Note the multiple hypopigmented follicular macules on the thighs. (F) These are also visible on a dermoscopic view.

• 

  Fig. 2 Histopathological findings of the only mature hair in the occipital region, the hypopigmented macules on the right thigh, and a follicular papule on the left knee. (A) On the scalp, there are a few vellus hairs and mild perivascular lymphocytic infiltration around the infundibulum and isthmus of the only mature hair. There is no inflammation around the hair bulb (H&E, ×40). (B) There is a loss of hair follicles on the thigh, with remnant arrector pili muscles. There are no marked changes in pigmentation, including melanin and melanocytes, of the basal layer of the epidermis (H&E, ×40). (C) The keratinous cysts in the skin over the knee contain laminated fine eosinophilic keratinous material and a granular layer in the cystic epithelium, compatible with an epidermal inclusion cyst (H&E, ×40).

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  Fig. 3 The DNA sequence of exon 5 of the HR gene. The arrow indicates the novel G-to-A transition at nucleotide position 191 in exon 5 of the gene on chromosome 8p12. This missense mutation results in the replacement of a glycine residue by a glutamate and is called G64E.

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  Fig. 4 Family pedigree. Circles and squares represent females and males, respectively. The solid square indicates the affected proband, and the half-filled figures indicate carriers. Individuals denoted by a cross (+) donated blood for DNA analysis.

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