Atypical Phacomatosis Pigmentokeratotica as the Expression of a Mosaic RASopathy With the BRAF-Glu586Lys Mutation

Ayala, D.; Ramón,; Martín, J.M.; Jordá, Esperanza

doi:10.1016/j.adengl.2016.02.008

Cited by 2 publications

(4 citation statements)

References 12 publications

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“…9 Other mutations like KRAS-and BRAF-mutation in Ras-Raf-MEK-ERK pathway are detected. 10 However, Happle et al…”

Section: Discussionmentioning

confidence: 99%

“…HRAS c.37G>C (p.G13R) mutation is reported in tumor tissue from both microdissected components of the keratinocytic adnexal and melanocytic tumor 9 . Other mutations like KRAS‐ and BRAF‐ mutation in Ras–Raf–MEK–ERK pathway are detected 10 . However, Happle et al believe that the KRAS‐ and BRAF ‐mutation cases do not feature a clear‐cut PPK, thus HRAS gene is the only proven cause of PPK 11 .…”

Section: Discussionmentioning

confidence: 99%

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The first case of Chinese phacomatosis pigmentokeratotica diagnosed by a missense HRAS mosaicism

Huang

Zhang

Chen

et al. 2022

The Journal of Dermatology

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Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus (EN) syndrome, featured by co‐occurrence of speckled lentiginous nevus (SLN) and nevus sebaceous (NS). The underlying mechanism has not been clarified. Pathogenic mutations in HRAS, KRAS and BRAF gene are recently recognized as the genetic cause of PPK. Here we present a case of Chinese PPK with a mosaic mutation in HRAS gene. Physical examination of the 4‐year‐old male proband showed NS locating on the scalp, with EN and SLN on trunk and extremities. Except congenital fundus vascular tortuosity, no evidence of extracutaneous abnormalities was found in this case. A rare heterozygous missense c. 181 C>A mosaic mutation in HRAS was identified in samples from NS, EN and pigmented nevus using next‐generation sequencing and Sanger sequencing. Meanwhile, no mutation was found in the non‐lesion skin, hair follicle, or blood DNA. Recent breakthrough in clinical manifestation, genetic mutation and prognosis of PPK is also reviewed.

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“…9 Other mutations like KRAS-and BRAF-mutation in Ras-Raf-MEK-ERK pathway are detected. 10 However, Happle et al…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The first case of Chinese phacomatosis pigmentokeratotica diagnosed by a missense HRAS mosaicism

Huang

Zhang

Chen

et al. 2022

The Journal of Dermatology

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“…The term mosaic is used in medicine to define organisms that are composed of at least two different genetic populations originating from a homogeneous zygote. 1,3,4 PPK is an explicit example of this phenomenon, as it is characterized by the association of an epidermal naevus and an SLN. Frequently patients show extracutaneous manifestations such as neurological, skeletal, cardiac, ocular or metabolic features.…”

Section: Discussionmentioning

confidence: 99%

“…They argued that a single activating dominant HRAS mutation in heterozygosity was responsible for the appearance of both the cutaneous and extracutaneous manifestations of PPK. 3,10 However, this may not be completely accurate, because since that initial description five more cases of PPK with available genetic analysis have been reported, 4,6,7,11,12 two of them showing BRAF 4,12 and one showing KRAS mutation. 6 Nevertheless, as those alterations involve the Ras-Raf-MEK-ERK pathways, we can affirm that PPK is a mosaic RASopathy, as are SN and epidermal keratinocytic naevus or Schimmelpenning syndrome, among others.…”

Section: Discussionmentioning

confidence: 99%

Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

et al. 2018

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A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his right face and scalp and a speckled lentiginous naevus (SLN) on his left trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions, which were contiguous with the upper-lip SN lesions. He also showed extracutaneous manifestations including cardiac, musculoskeletal and ocular alterations. Internally, he had developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, oral papillomatous hyperplasia and both rhabdomyosarcomas were analysed by Sanger sequencing. An HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA were wild-type. Phacomatosis pigmentokeratotica (PPK) is characterized by the association of an SN with a papular naevus spilus and extracutaneous manifestations. Until recently, the aetiopathogenetic hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASopathies. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, an HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of an HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Furthermore, the HRAS c.37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand in a privileged position of being able to detect these alterations.

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Atypical Phacomatosis Pigmentokeratotica as the Expression of a Mosaic RASopathy With the BRAF-Glu586Lys Mutation

Cited by 2 publications

References 12 publications

The first case of Chinese phacomatosis pigmentokeratotica diagnosed by a missense HRAS mosaicism

The first case of Chinese phacomatosis pigmentokeratotica diagnosed by a missense HRAS mosaicism

Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

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