Dermatopathology and Molecular Genetics

February 2008 in “ Journal of The American Academy of Dermatology ”

Reuven Bergman

epidermolysis bullosa ectodermal dysplasia/skin fragility syndrome congenital alopecias immunohistochemistry KRT5 KRT14 PKP1 CDH3 hypotrichosis with juvenile macular dystrophy vitamin D receptor VDR hairless gene EB EDSFS HJMD

Studysummary This review discusses recent advances in molecular genetics and their impact on the accuracy and understanding of diagnosing inherited skin diseases but reports no new results.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

In the 2008 review, the integration of dermatopathology and molecular genetics was shown to have significantly improved the diagnosis and understanding of inherited skin diseases, including epidermolysis bullosa (EB), ectodermal dysplasia/skin fragility syndrome (EDSFS), and congenital alopecias. Immunohistochemistry on paraffin sections was found to be effective in diagnosing EB, with an 85% diagnostic rate in a study of 39 cases. Histopathologic clues were used to identify mutations in genes like KRT5, KRT14, and PKP1. Advances in molecular genetics have also led to more precise classifications of congenital alopecias, with mutations in the CDH3 gene identified as the cause of hypotrichosis with juvenile macular dystrophy (HJMD). Similar clinical and histologic features in alopecias associated with mutations in the vitamin D receptor (VDR) and the hairless gene suggest an interaction between these genes. The review underscores the enhanced role of dermatopathology in diagnosing skin diseases due to molecular genetics.

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Research cited in this study

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research Histopathological and Ultrastructural Study of Ectodermal Dysplasia/Skin Fragility Syndrome

31 citations , August 2005 in “The American Journal of Dermatopathology”

This study investigated the histopathology of ectodermal dysplasia/skin fragility syndrome, identifying specific skin and hair abnormalities associated with PKP1 gene mutations in two young female patients.

research Ligand-Independent Actions of the Vitamin D Receptor Maintain Hair Follicle Homeostasis

144 citations , December 2004 in “Molecular Endocrinology”

This study found that the effects of the vitamin D receptor on hair follicle cycling in mice are independent of its ability to bind a hormone, with specific domain mutations influencing hair regrowth outcomes.

research Histopathology of Hypotrichosis with Juvenile Macular Dystrophy

19 citations , May 2004 in “The American Journal of Dermatopathology”

In this study, scalp biopsies from HJMD patients revealed histological similarities to chronic telogen effluvium and highlighted the role of CDH3 mutations disrupting normal hair cycles.

research Phenotypic Diversity and Mutation Spectrum in Hypotrichosis with Juvenile Macular Dystrophy

52 citations , November 2003 in “Journal of Investigative Dermatology”

In this study, mutations in the CDH3 gene were identified as the cause of hypotrichosis with juvenile macular dystrophy, and the researchers observed substantial phenotypic variability among affected individuals.

research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

research Clinical and Molecular Diagnostic Criteria of Congenital Atrichia with Papular Lesions

69 citations , May 2002 in “Journal of Investigative Dermatology”

This study suggests that congenital atrichia with papular lesions may be more common than previously thought and proposes diagnostic criteria including the observation of hypopigmented whitish streaks on the scalp.

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”

This case report describes a patient with mutations in both alleles of the vitamin D receptor who exhibited hair loss clinically indistinguishable from generalized atrichia with papules, suggesting a potential genetic pathway shared with the hairless gene.

research A Novel Missense Mutation (C622G) in the Zinc-Finger Domain of the Human Hairless Gene Associated with Congenital Atrichia with Papular Lesions

47 citations , April 2000 in “Experimental Dermatology”

This study identified a novel missense mutation in the hairless gene in a Polish family, which may contribute to congenital atrichia with papular lesions by affecting the gene's function.

research Novel Hairless Mutations in Two Kindreds with Autosomal Recessive Papular Atrichia

66 citations , December 1999 in “Journal of Investigative Dermatology”

New mutations in the hairless gene may cause hair loss and affect bone development.

research A Homozygous Nonsense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia

37 citations , August 1999 in “Journal of Investigative Dermatology”

This study identified a nonsense mutation in the zinc-finger domain of the hairless gene associated with congenital atrichia in a Japanese family, indicating a potential genetic cause for this rare form of alopecia.

research The Role of the Hairless (Hr) Gene in the Regulation of Hair Follicle Catagen Transformation

166 citations , July 1999 in “American Journal Of Pathology”

This study found that the loss of a functional hr gene in mice leads to premature and abnormal hair follicle regression, disrupting normal hair cycling and architecture.

research Atrichia and Papular Lesions: Report of a Case

18 citations , January 1992 in “Dermatology”

This case report details atrichia with papular lesions in a 4-year-old girl, highlighting specific histological findings on her scalp and other affected areas.