Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi.
Cafe-au-Lait Spots
/ diagnosis
Child
DNA Mutational Analysis
Female
GTP Phosphohydrolases
/ genetics
Genetic Testing
Humans
Membrane Proteins
/ genetics
Mosaicism
Neoplasms, Multiple Primary
/ diagnosis
Neurofibroma, Plexiform
/ diagnosis
Neurofibromatosis 1
/ complications
Neurofibromin 1
/ genetics
Nevus, Pigmented
/ diagnosis
Skin
/ pathology
Skin Neoplasms
/ diagnosis
café-au-lait spots
mosaicism
neurofibromatosis 1
pigmented nevus
plexiform neurofibroma
Journal
The Journal of dermatology
ISSN: 1346-8138
Titre abrégé: J Dermatol
Pays: England
ID NLM: 7600545
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
04
02
2020
accepted:
02
03
2020
pubmed:
5
4
2020
medline:
16
3
2021
entrez:
5
4
2020
Statut:
ppublish
Résumé
Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.
Identifiants
pubmed: 32246533
doi: 10.1111/1346-8138.15327
doi:
Substances chimiques
Membrane Proteins
0
NF1 protein, human
0
Neurofibromin 1
0
GTP Phosphohydrolases
EC 3.6.1.-
NRAS protein, human
EC 3.6.1.-
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
658-662Subventions
Organisme : Sapporo Medical University
Informations de copyright
© 2020 Japanese Dermatological Association.
Références
Thappa DM, Jeevankumar B, Karthikeyan K. Giant café-au-lait macule in neurofibromatosis type 1. J Dermatol 2001; 28: 60-61.
Schaffer JV, Chang MW, Kovich OI, Kamino H, Orlow SJ. Pigmented plexiform neurofibroma: Distinction from a large congenital melanocytic nevus. J Am Acad Dermatol 2007; 56: 862-868.
Maruoka R, Takenouchi T, Torii C et al. The use of next-generation sequencing in molecular diagnosis of neurofibromatosis type 1: a validation study. Genet Test Mol Biomarkers 2014; 18: 722-735.
De Schepper S, Maertens O, Callens T, Naeyaert JM, Lambert J, Messiaen L. Somatic mutation analysis in NF1 café au lait spots reveals two NF1 hits in the melanocytes. J Invest Dermatol 2008; 128: 1050-1053.
Tanito K, Ota A, Kamide R, Nakagawa H, Niimura M. Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1. J Dermatol 2014; 41: 724-728.
Ball NJ, Kho GT. Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas: a study of 226 cases. J Cutan Pathol 2005; 32: 523-532.
Maize JC, Burch HW. Dysplastic nevi with an underlying or juxtaposed neurofibroma: does a relationship exist? J Cutan Pathol 2007; 34: 837-843.
Harder A, Tippmar M, Baschinskij S, Rancso C, Janda J, Mairinger T. Do juxtaposed compound nevus and neurofibroma with melanocytic differentiation share an identical cell of origin in NF1? Eur J Dermatol 2015; 25: 615-617.
Gutmann DH, Aylsworth A, Carey JC et al. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 1997; 278: 51-57.
Idogawa M, Hida T, Tanaka T et al. Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH). Cancer Biol Ther 2020; 21: 315-319.
Yang FC, Ingram DA, Chen S et al. Nf1-dependent tumors require a microenvironment containing Nf1+/- and c-kit-dependent bone marrow. Cell 2008; 135: 437-448.
Maertens O, De Schepper S, Vandesompele J et al. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet 2007; 81: 243-251.
Fetsch JF, Michal M, Miettinen M. Pigmented (melanotic) neurofibroma: a clinicopathologic and immunohistochemical analysis of 19 lesions from 17 patients. Am J Surg Pathol 2000; 24: 331-343.
Dupin E, Real C, Glavieux-Pardanaud C, Vaigot P, Le Douarin NM. Reversal of developmental restrictions in neural crest lineages: transition from Schwann cells to glial-melanocytic precursors in vitro. Proc Natl Acad Sci U S A 2003; 100: 5229-5233.
Roh MR, Eliades P, Gupta S, Tsao H. Genetics of melanocytic nevi. Pigment Cell Melanoma Res 2015; 28: 661-672.