A Study of Immunohistochemical and Electron Microscopic Changes in Dowling‐Degos Disease

Zhang, Ru‐Zhi; Zhu, Weiming

doi:10.1111/j.1346-8138.2005.tb00706.x

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…The affected individuals had spotted and reticulate pigmentation of the flexures (Figure 1). The immunohistochemistry and electron microscopy of lesions from patients with RPAF can be seen in our study (Zhang and Zhu, 2005).…”

Section: Clinical Findingsmentioning

confidence: 72%

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A Gene Locus Responsible for Reticulate Pigmented Anomaly of the Flexures Maps to Chromosome 17p13.3

Xing

et al. 2006

Journal of Investigative Dermatology

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Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted and reticulate pigmentation of the flexures. The gene, or even the chromosomal location, for RPAF has not yet been identified. In this study, one Chinese family with RPAF was identified and subjected to a genomewide screen for linkage analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination fraction theta=0.00). Haplotype analyses indicated that the disease gene is located within the 6.8 cM region distal to D17S1798. It is the first locus identified for RPAF. This study provides a map location for isolation of a disease gene causing RPAF.

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Section: Clinical Findingsmentioning

confidence: 72%

“…It showed an autosomaldominant inheritance pattern and was ascertained by the First Affiliated Hospital of Nanjing Medical University. Clinical, histological, and electron microscopic characteristics supported the diagnosis of RPAF (Zhang and Zhu, 2005). The study was conducted according to The Declaration of Helsinki Principles.…”

Section: Subjectsmentioning

confidence: 99%

A Gene Locus Responsible for Reticulate Pigmented Anomaly of the Flexures Maps to Chromosome 17p13.3

Xing

et al. 2006

Journal of Investigative Dermatology

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“…Acanthosis and hyperpigmentation with the presence of large melanosomes in HPX were reminiscent of features described in patients with DDD (Grosshans et al, ; Zhang & Zhu, ). Such patients have activating mutations in keratin 5.…”

Section: Resultsmentioning

confidence: 57%

“…Mutations in genes directly involved in pigmentation (c‐kit, tyrosinase, TRP‐1, MATP or P gene) have been identified in hypopigmented diseases such as piebaldism and albinism, while mutations in cytoskeletal proteins (keratin 5, 14) have been identified in hyperpigmented diseases such as DDD (Liao et al, ), Galli–Gali disease (Reisenauer et al, ), epidermolysis bullosa associated with mottled pigmentation (EBS‐MP) (Geller, Kristal, & Morel, ; Horiguchi et al, ; Irvine, McKenna, Jenkinson, & Hughes, ), Naegeli–Franceschetti–Jadassohn syndrome, and dermatopathia pigmentosa reticularis (Lugassy et al, ). Interestingly, Grosshans and colleagues and Zhang and Zhu (Grosshans, Geiger, Hanau, Jelen, & Heid, ; Zhang & Zhu, ) using electron microscopy observed a large number of single melanosomes characteristic of phototype VI skin in the lesional skin of patients with DDD.…”

Section: Introductionmentioning

confidence: 99%

Epidermal keratin 5 expression and distribution is under dermal influence

Cario‐André

Pain

Kaulanjan-Checkmodine

et al. 2019

Pigment Cell Melanoma Res

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Human skin melanin pigmentation is regulated by systemic and local factors. According to the type of melanin produced by melanocytes, the transfer and degradation of melanosomes differ, thus accounting for most variations between ethnicities. We made the surprising observation that in a drastically changed environment, white and black phenotypes are reversible since Caucasian skin grafted onto nude mice can become black with all black phenotypic characteristics. Black xenografts differed essentially from other grafts by the levels of epidermal FGF‐2 and keratin 5. In vitro analysis confirmed that FGF‐2 directly regulates keratin 5. Interestingly, this phenomenon may be involved in human pathology. Keratin 5 mutations in Dowling–Degos Disease (DDD) have already been associated with the pheomelanosome–eumelanosome transition. In a DDD patient, keratin 5 was expressed in the basal and spinous layers, as observed in black xenografts. Furthermore, in a common age‐related hyperpigmentation disorder like senile lentigo (SL), keratin 5 distribution is also altered. In conclusion, modulation of keratin 5 expression and distribution either due to mutations or factors may account for the development of pigmentary disorders.

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“…of the disease. 42,43 Therefore, we can hypothesize that other biological activities of NCSTN may be responsible for DDD in these patients as it is known that NCSTN is localized in melanosome membranes in all their maturation stages 44 and its role in their biogenesis and degradation requires a deeper investigation. We can also conjecture that the deficiency of NCSTN mature form led to the degradation of other gamma-secretase subunits such as PSEN-1, PSEN-2 and PSENEN.…”

Section: Discussionmentioning

confidence: 99%

A loss‐of‐function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa

de Oliveira,

de Siqueira,

Nait‐Meddour

et al. 2023

Experimental Dermatology

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Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT‐1 and POFUT‐1 genes have been associated with DDD, and loss‐of‐function mutations in PSENEN, a subunit of the gamma‐secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma‐secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four‐generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense‐mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma‐secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co‐occurrence in HS patients carrying a mutation in the NCSTN gene.

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A Study of Immunohistochemical and Electron Microscopic Changes in Dowling‐Degos Disease

Cited by 7 publications

References 11 publications

A Gene Locus Responsible for Reticulate Pigmented Anomaly of the Flexures Maps to Chromosome 17p13.3

A Gene Locus Responsible for Reticulate Pigmented Anomaly of the Flexures Maps to Chromosome 17p13.3

Epidermal keratin 5 expression and distribution is under dermal influence

A loss‐of‐function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa

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