A Novel Missense Mutation Affecting the Human Hairless Thyroid Receptor Interacting Domain 2 Causes Congenital Atrichia

October 2002 in “ Journal of Investigative Dermatology ”

Izabella Klein, Reuven Bergman, M. Indelman, Eli Sprecher

The study identified a novel missense mutation in the hairless (hr) gene, specifically a G to A transition at cDNA position 3034, resulting in a D1012N substitution, which was linked to congenital atrichia in a 17-year-old female with alopecia universalis congenita. This mutation was homozygous in the patient, heterozygous in her mother, and absent in her sister, and was not found in 326 chromosomes from healthy individuals, indicating it was not a common polymorphism. The mutation affected the hairless thyroid receptor interacting domain 2, crucial for binding to the thyroid hormone receptor, underscoring its functional importance. The findings enhanced the understanding of the genetic basis of congenital alopecias and the role of the hr gene, with implications for diagnosing hr-related disorders.

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research The Hairless Gene in Androgenetic Alopecia: Results of a Systematic Mutation Screening and a Family-Based Association Approach

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research Atrichia Caused by Mutations in the Vitamin D Receptor Gene Is a Phenocopy of Generalized Atrichia Caused by Mutations in the Hairless Gene

139 citations, September 2001 in “The journal of investigative dermatology/Journal of investigative dermatology”

Mutations in the Vitamin D receptor gene can cause hair loss similar to mutations in the Hairless gene.

research Variant 1859G→A (Arg620Gln) of the Hairless Gene: Absence of Association with Papular Atrichia or Androgenetic Alopecia

14 citations, July 2001 in “American Journal of Human Genetics”

Haplogroup X found in Altaian population supports Amerindian origin.

research Towards a Molecular Understanding of Hair Loss and Its Treatment

236 citations, July 2001 in “Trends in Molecular Medicine”

Future hair loss treatments should aim to extend hair growth, reactivate resting follicles, reverse shrinkage, and possibly create new follicles, with gene therapy showing promise.

research Molecular and Functional Aspects of the Hairless (Hr) Gene in Laboratory Rodents and Humans

126 citations, October 1998 in “Experimental Dermatology”

The document discussed the hairless (hr) gene in laboratory rodents and humans, highlighting its role in skin physiology and hair follicle biology. Although hairless and rhino mouse mutants were extensively used to study skin-related topics, the primary cellular defect of hairlessness was often overlooked. The identification of the human homolog of the hr gene on Chromosome 8p12 linked it to a congenital hair disorder in humans, similar to hairless mice. Mutations in the hr gene in mice served as models for understanding its function and the pathophysiology of related human disorders. The document reviewed the structure, expression patterns, and mutations of the hr gene, as well as associated pathologies, reproductive and immunological defects, and susceptibility to dioxin toxicity. It speculated on the potential functions of the hr gene product in skin and hair follicle biology.

research Modulation of Murine Hair Follicle Function by Alterations in Ornithine Decarboxylase Activity

71 citations, May 1996 in “Journal of Investigative Dermatology”

The study investigated the role of ornithine decarboxylase (ODC) in hair follicle function using transgenic mice that overexpressed a mutated ODC transgene in hair follicle keratinocytes. These mice experienced normal initial hair growth but lost their hair completely 2-3 weeks after birth, coinciding with the onset of ODC overexpression and the development of follicular cysts. The study found that the ODC inhibitor 2-difluoromethylornithine could prevent hair loss and partially restore normal skin histology if administered early, and it could also reactivate hair growth in mice with complete hair loss. The results suggested that ODC played a crucial regulatory role in mouse hair follicles.