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

Li, Chengrang; Xing, Qinghe; Li, Ming; Qin, Wei; Yue, Xue-Zhuang; Zhang, Xiaoju; Ma, Huijun; Wang, Daguang; Gao, Feng; Zhu, Weiming; He, Lin

doi:10.1038/sj.jid.5700271

Cited by 26 publications

(21 citation statements)

References 37 publications

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“…Li et a I. (7) mapped this disorder to chromosome 17pl3.3 in a Chinese family, and Betz et al (3) to chromosome 12q in two German families. In the latter report, two loss-of-function mutations were identified in exon 1 ofthe KRT5 gene, leading to the truncation of KRT5 protein before the rod domain, in all affected family members and in six of an additional eight unrelated Caucasian patients with DDD.…”

Section: Case Reportmentioning

confidence: 96%

Dowling-Degos Disease with Asymmetrical Axillary Distribution and No KRT 5 Exon 1 Mutation

Asahina¹,

Ishii²,

Kai³

et al. 2007

Acta Derm Venereol

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Dowling-Degos disease (DDD) is a rare disorder characterized by acquired pigniented maeules and papules in a reticulate pattern, particularly affecting the flexural areas and other major skin folds (I, 2). A female patient presented with dotted and reticulate pigmentation ofthe axilla, and was diagnosed as DDD both clinically and histopathologically. However, the asymmetrical distribution ofthe eruption was distinct from classical DDD. In contrast to recent reports in Caucasian patients with DDD (3,4), we found no evidence of mutation of exon 1 ofthe keratin 5 (KRT5) gene, suggesting an aetiological heterogeneity of this disorder. CASE REPORTA 47-year-old Japanese woman presented at our department with development of reticulate pigmentation on her axilla. She had first noticed dotted pigmentation on her left axilla 8 years previously, which had gradually increased and coalesced. Similar pigmentation subsequently emerged on her right axilla 2 years previously. There were no clinical symptoms, such as pruritus, and she had no axillary hyperhidrosis. On examination, miliary brown macules and papules were seen distributed over the vault of her axilla, coalescing to give rise to reticulated patches. The lesion on the left side was more pronounced than that on the right (Fig. 1). The eruptions were slightly hyperkeratotic, with no apparent scaling on the surface. Some macules were in linear alignment, suggesting the presence of Koebner's phenomenon. The patient was otherwise healthy. There was no pigmentation in other areas, such as the groin, neck or other flexures. No other family members had pigmentary abnormalities. A biopsy specimen from the early lesion on the right axilla showed slight orthokeratosis and acanthosis. characterized by irregular elongation of rete ridges and basal hyperpigmentation (Fig. 2). There was no papilloniatosis. A subsequent biopsy from the older lesion on the left side showed an identical histological picture (not shown). Slight oedema and infiltration of lymphocytes around capillaries were seen in the upper dermis. Considering the characteristic clinical picture and the histopathological findings, a diagnosis of DDD was made. Repeated cryosurgery using liquid nitrogen was partially effective in resolving the lesion (not shown).DISCUSSION DDD (1.2) usually presents in adults, commonly women, and most frequently during the fourth decade of life. Although DDD is usually inherited in an autosomal dominant fashion, some sporadic cases have been reported, as in our patient. The axilla and groin arc the most common sites, but other areas may be involved, including the intergluteal and infra-mammary folds, neck, scalp, trunk and arms. Other possible cutaneous manifestations include perioral pitted scars and comedo-like lesions on the neck and back. Occasional Fig. ]. (a) Muitiple, small brown macules and papules in relicular distribution localized on tbe axilla. The lesion on tbe left side was more pronouneed tban tliat on ibe rigbt. (b) Ciose-up ol' Ibc lell axilla.

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Section: Case Reportmentioning

confidence: 96%

Dowling-Degos Disease with Asymmetrical Axillary Distribution and No KRT 5 Exon 1 Mutation

Asahina¹,

Ishii²,

Kai³

et al. 2007

Acta Derm Venereol

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“…Another larger linkage analysis from a 4-generation Chinese family showed a possible DDD-related gene locus mapping to chromosome 17p13.3. 22 Several genes are located in this region, however, and no particular candidate gene or sequence affecting pigmentation was recognized. Looking at the problem from a different angle, we note that DSH has recently been mapped to chromosome 1q21, 14 with pathogenic mutations located in the DSRAD gene.…”

Section: Casementioning

confidence: 98%

“…3 have been described recently in cases of DDD. 21,22 We reported a family with autosomal dominant inheritance (Fig 1) of a skin disorder with clinical features of both DDD and DUH (Figs 2 and 3). …”

mentioning

confidence: 95%

Generalized Dowling-Degos disease

Lin

2007

Journal of the American Academy of Dermatology

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“…6,10,11 Another locus for DDD was identified in an affected Chinese family; this locus is on chromosome 17p13.3, but the responsible mutation has not been identified to date. 12 Additionally, recent studies of two Chinese families with DDD led to the identification of mutations in POFUT1 (MIM 607491), which encodes protein O-fucosyltransferase 1 from the Notch pathway. 13 Here, we describe the identification of nine different mutations in POGLUT1 (RefSeq accession number NM_152305.2) from 13 unrelated individuals with DDD.…”

Section: Dowling-degos Disease (Ddd [Mim 179850 Mim 615327])mentioning

confidence: 99%

Mutations in POGLUT1, Encoding Protein O-Glucosyltransferase 1, Cause Autosomal-Dominant Dowling-Degos Disease

Basmanav

Oprişoreanu

Pasternack

et al. 2014

The American Journal of Human Genetics

141

153

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Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To identify additional causes of DDD, we performed exome sequencing in five unrelated affected individuals without mutations in KRT5. Data analysis identified three heterozygous mutations from these individuals, all within the same gene. These mutations, namely c.11G>A (p.Trp4*), c.652C>T (p.Arg218*), and c.798-2A>C, are within POGLUT1, which encodes protein O-glucosyltransferase 1. Further screening of unexplained cases for POGLUT1 identified six additional mutations, as well as two of the above described mutations. Immunohistochemistry of skin biopsies of affected individuals with POGLUT1 mutations showed significantly weaker POGLUT1 staining in comparison to healthy controls with strong localization of POGLUT1 in the upper parts of the epidermis. Immunoblot analysis revealed that translation of either wild-type (WT) POGLUT1 or of the protein carrying the p.Arg279Trp substitution led to the expected size of about 50 kDa, whereas the c.652C>T (p.Arg218*) mutation led to translation of a truncated protein of about 30 kDa. Immunofluorescence analysis identified a colocalization of the WT protein with the endoplasmic reticulum and a notable aggregating pattern for the truncated protein. Recently, mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were also reported to be responsible for DDD. Interestingly, both POGLUT1 and POFUT1 are essential regulators of Notch activity. Our results furthermore emphasize the important role of the Notch pathway in pigmentation and keratinocyte morphology.

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

Cited by 26 publications

References 37 publications

Dowling-Degos Disease with Asymmetrical Axillary Distribution and No KRT 5 Exon 1 Mutation

Dowling-Degos Disease with Asymmetrical Axillary Distribution and No KRT 5 Exon 1 Mutation

Generalized Dowling-Degos disease

Mutations in POGLUT1, Encoding Protein O-Glucosyltransferase 1, Cause Autosomal-Dominant Dowling-Degos Disease

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