Update of recent findings in genetic hair disorders

Shimomura, Yutaka

doi:10.1111/1346-8138.16204

Cited by 14 publications

(21 citation statements)

References 129 publications

(369 reference statements)

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“…1 These conditions share a number of clinical features, 1 including blister formation as found in epidermolysis bullosa simplex, 7 hyperkeratosis as exemplified by epidermolytic hyperkeratosis, 8 nail dystrophy as demonstrated in pachyonychia congenita 9 and hair abnormalities as typical of monilethrix. 10 The present observations delineate a unique phenotype combining all of the cardinal features of keratin disorders. Desmosomal disorders such as ectodermal dysplasia with skin fragility can occasionally mimic the clinical features of these conditions, most probably owing to the fact that the function of keratin filaments is in part dependent upon their ability to interact with the desmosomal plaque.…”

Section: Discussionmentioning

confidence: 58%

“…Keratinopathies result from pathogenic variants in genes encoding keratin proteins expressed in the skin and mucosae and their appendages 1 . These conditions share a number of clinical features, 1 including blister formation as found in epidermolysis bullosa simplex, 7 hyperkeratosis as exemplified by epidermolytic hyperkeratosis, 8 nail dystrophy as demonstrated in pachyonychia congenita 9 and hair abnormalities as typical of monilethrix 10 . The present observations delineate a unique phenotype combining all of the cardinal features of keratin disorders.…”

Section: Discussionmentioning

confidence: 61%

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A unique skin phenotype resulting from a large heterozygous deletion spanning six keratin genes

Mohamad

Sarig

Beattie

et al. 2022

British Journal of Dermatology

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The phenotypic spectrum of genodermatoses is continuously expanding. Three siblings were referred because of a highly unusual phenotype comprising alopecia, dystrophic nails, palmoplantar keratoderma and trauma‐induced skin blistering. Whole‐exome sequencing analysis identified a heterozygous large genomic alteration of around 116 0000 bp resulting in the deletion of the KRT9, KRT14, KRT15, KRT16 and KRT19 genes, as well as part of KRT17. This genomic change leads to the generation of a truncated keratin 17 (KRT17) protein encoded by the first three exons of the gene and part of intron 3. The three patients were found to carry the heterozygous genomic deletion while their healthy parents did not, indicative of germline mosaicism. The genomic alteration was found to result in reduced KRT17 expression in patient skin. More importantly, the abnormal truncated KRT17 was found to exert a deleterious effect on keratinocyte cytoskeleton formation, leading to keratin aggregation. Coexpression of wildtype and truncated KRT17 proteins also caused keratin aggregation, demonstrating that the deletion exerts a dominant negative effect. In conclusion, we are reporting on a novel clinical phenotype that was found to result from germline mosaicism for a large genomic deletion spanning six keratin genes, thus expanding the spectrum of clinical manifestations associated with keratin disorders. What is already known about this topic? Various conditions known as keratinopathies have been shown over recent years to be associated with dominant or recessive variants in several individual keratin genes. What does this study add? We report three patients presenting with a unique clinical phenotype that was found to result from germline mosaicism for a large genomic deletion spanning six keratin genes. The genomic variant is predicted to result in a truncated form of keratin 17, which was found in an in vitro assay to disrupt keratinocyte cell cytoskeleton formation.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 61%

A unique skin phenotype resulting from a large heterozygous deletion spanning six keratin genes

Mohamad

Sarig

Beattie

et al. 2022

British Journal of Dermatology

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“…1 LIPH and other genes in which lossof-function mutations are detected in ARWH/H are involved in a signaling pathway that is critical for hair follicle development and growth. [1][2][3] The mutation c.742C > A in LIPH has been reported to be pathogenic for ARWH/H by in vitro assays. 4 A previous study reported that the mutation c.614A > G, which is highly conserved among different species (Figure 1e), led to impaired secretion of PA-PLA1α, which contributed to the development of ARWH/H.…”

Section: Letter To the Editormentioning

confidence: 99%

“…The disease is caused by mutations in LIPH, LPAR6 (also known as P2RY5), KRT25, or C3ORF52. [1][2][3] We describe a patient with ARWH/H who carried compound heterozygous mutations in the LIPH gene at c.742C > A and c.614A > G.…”

mentioning

confidence: 99%

Case of autosomal recessive woolly hair/hypotrichosis with compound heterozygous mutations in the LIPH gene at c.742C > A and c.614A > G: The first Japanese case

Yamaguchi

Kiniwa

Abe

et al. 2023

The Journal of Dermatology

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“…Alopecia universalis is rare, but early balding may occur. Eyebrows and eyelashes are also sparse or absent [ 25 ]. The hair phenotype can be further investigated by trichoscopy and light microscopy [ 26 ].…”

Section: Phenotypementioning

confidence: 99%

Molecular Pathway-Based Classification of Ectodermal Dysplasias: First Five-Yearly Update

Peschel

Wright

Koster

et al. 2022

Genes

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To keep pace with the rapid advancements in molecular genetics and rare diseases research, we have updated the list of ectodermal dysplasias based on the latest classification approach that was adopted in 2017 by an international panel of experts. For this purpose, we searched the databases PubMed and OMIM for the term “ectodermal dysplasia”, referring mainly to changes in the last 5 years. We also tried to obtain information about those diseases on which the last scientific report appeared more than 15 years ago by contacting the authors of the most recent publication. A group of experts, composed of researchers who attended the 8th International Conference on Ectodermal Dysplasias and additional members of the previous classification panel, reviewed the proposed amendments and agreed on a final table listing all 49 currently known ectodermal dysplasias for which the molecular genetic basis has been clarified, including 15 new entities. A newly reported ectodermal dysplasia, linked to the gene LRP6, is described here in more detail. These ectodermal dysplasias, in the strict sense, should be distinguished from syndromes with features of ectodermal dysplasia that are related to genes extraneous to the currently known pathways involved in ectodermal development. The latter group consists of 34 syndromes which had been placed on the previous list of ectodermal dysplasias, but most if not all of them could actually be classified elsewhere. This update should streamline the classification of ectodermal dysplasias, provide guidance to the correct diagnosis of rare disease entities, and facilitate the identification of individuals who could benefit from novel treatment options.

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Update of recent findings in genetic hair disorders

Cited by 14 publications

References 129 publications

A unique skin phenotype resulting from a large heterozygous deletion spanning six keratin genes

A unique skin phenotype resulting from a large heterozygous deletion spanning six keratin genes

Case of autosomal recessive woolly hair/hypotrichosis with compound heterozygous mutations in the LIPH gene at c.742C > A and c.614A > G: The first Japanese case

Molecular Pathway-Based Classification of Ectodermal Dysplasias: First Five-Yearly Update

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