Hairless Gene Nonsense Mutations in Alopecia Universalis: A Case Report
Alopecia universalis (AU) congenital, known as generalized atrichia, is a severe form of autosomal recessive alopecia that results in complete hair loss of scalp and body. Mutations in the human hairless gene (HR) are associated with the phenotype of the disease. A consanguineous couple who had a child with the generalized atrichia sign referred to us for genetic counseling. According to the patient's symptoms and after thorough examination and history taking, the HR gene was the candidate gene to be assessed and analyzed. For this purpose targeted primers were designed for all exons of the HR gene followed by running PCR for exons amplification. Finally, the PCR products were sequenced. Whole-gene sequence analysis revealed a nonsense homozygous mutation in exon 6 that, according to the ACMG guide, is a pathogenic variant. Sequence analysis of the exon in parents reveals that they are heterozygout for the non-sense mutation, as well.
2. Lee S, Paik SH, Kim H-J, et al (2013). Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis. PLoS One, 8(1):e53613.
3. Nöthen MM, Cichon S, Vogt IR, et al (1998). A gene for universal congenital alopecia maps to chromosome 8p21-22. Am J Hum Genet, 62(2):386-90.
4. Mann SJ (1971). Hair loss and cyst formation in hairless and rhino mutant mice. Anat Rec, 170(4):485-99.
5. Bolduc C, Lui H, Shapiro J (2006). Alopecia areata. E-Medicine from WebMD.
6. Potter GB, Beaudoin GM, DeRenzo CL, et al (2001). The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor. Genes Dev, 15(20):2687-2701.
7. Maatough A, Whitfield GK, Brook L, et al (2018). Human hairless protein roles in skin/hair and emerging connections to brain and other cancers. J Cell Biochem, 119(1):69-80.
8. Abbasi AA (2011). Molecular evolution of HR, a gene that regulates the postnatal cycle of the hair follicle. Sci Rep, 1:32.
9. Ahmad W, Irvine AD, Lam H, et al (1998). A missense mutation in the zinc-finger domain of the human hairless gene underlies congenital atrichia in a family of Irish travellers. Am J Hum Genet, 63(4):984-91.
10. Ahmad W, Zlotogorski A, Panteleyev AA, et al (1999). Genomic organization of the human hairless gene (HR) and identification of a mutation underlying congenital atrichia in an Arab Palestinian family. Genomics, 56(2):141-8.
11. Panteleyev A, Paus R, Ahmad W, et al (1998). Molecular and functional aspects of the hairless (hr) gene in laboratory rodents and humans. Exp Dermatol, 7(5):249-67.
12. Panteleyev AA, Botchkareva NV, van der Veen C, et al (1998). Pathobiology of the hairless phenotype: Dysregulation of hair follicle apoptosis and topobiology during the initiation of follicle cycling. Journal of Dermatological Science, 16:S105.
13. Panteleyev AA, van der Veen C, Rosenbach T, et al (1998). Towards defining the pathogenesis of the hairless phenotype. J Invest Dermatol, 110(6):902-7.
14. Hsieh J-C, Sisk JM, Jurutka PW, et al (2003). Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling. J Biol Chem, 278(40):38665-74.
15. Beaudoin GM, Sisk JM, Coulombe PA, et al (2005). Hairless triggers reactivation of hair growth by promoting Wnt signaling. Proc Natl Acad Sci U S A, 102(41):14653-8.
16. Henn W, Zlotogorski A, Lam H, et al (2002). Atrichia with papular lesions resulting from compound heterozygous mutations in the hairless gene: A lesson for differential diagnosis of alopecia universalis. J Am Acad Dermatol, 47(4):519-23.
17. Hug N, Longman D, Cáceres JF (2016). Mechanism and regulation of the nonsense-mediated decay pathway. Nucleic Acids Res, 44(4):1483-95.
|Issue||Vol 50 No 6 (2021)|
|Alopecia Human hairless gene Alopecia universalis|
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