Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

Tinschert, Sigrid; Naumann, Ilka; Stegmann, Elisabeth; Buske, Annegret; Kaufmann, Dieter; Thiel, Gundula; Jenne, Dieter E.

doi:10.1038/sj.ejhg.5200493

Cited by 209 publications

(116 citation statements)

References 19 publications

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“…Recently, molecular evidence has been provided for several mosaic cutaneous traits representing a type 1 segmental involvement, including epidermolytic hyperkeratosis of Brocq (21), neurofibromatosis type 1 (22), Darier disease (23,24), and Apert syndrome (25).…”

Section: Discussionmentioning

confidence: 99%

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept

Poblete‐Gutiérrez¹,

Wiederholt²,

König³

et al. 2004

J. Clin. Invest.

127

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Hailey-Hailey disease (HHD) is an autosomal dominant trait characterized by erythematous and oozing skin lesions preponderantly involving the body folds. In the present unusual case, however, unilateral segmental areas along the lines of Blaschko showing a rather severe involvement were superimposed on the ordinary symmetrical phenotype. Based on this observation and similar forms of mosaicism as reported in other autosomal dominant skin disorders, we postulated that in such cases, 2 different types of segmental involvement can be distinguished. Accordingly, the linear lesions as noted in the present case would exemplify type 2 segmental HHD. In the heterozygous embryo, loss of heterozygosity occurring at an early developmental stage would have given rise to pronounced linear lesions reflecting homozygosity or hemizygosity for the mutation. By analyzing DNA and RNA derived from blood and skin samples as well as keratinocytes of the index patient with various molecular techniques including RT-PCR, real-time PCR, and microsatellite analysis, we found a consistent loss of the paternal wild-type allele in more severely affected segmental skin regions, confirming this hypothesis for the first time, to our knowledge, at the molecular and cellular level.

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Section: Discussionmentioning

confidence: 99%

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept

Poblete‐Gutiérrez¹,

Wiederholt²,

König³

et al. 2004

J. Clin. Invest.

127

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“…The age of the 13 male patients ranged from 0 (birth) to 31 years, the age of the eight females from 2 to 45 years. The presence and extension of the NF1 microdeletions were determined as described by Tinschert et al 23 In all, 19…”

Section: Methodsmentioning

confidence: 99%

Childhood overgrowth in patients with common NF1 microdeletions

et al. 2005

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While growth retardation and short stature are well-known features of patients with classical neurofibromatosis type 1 (NF1), we found advanced height growth and accelerated carpal bone age in patients with an NF1 microdeletion. Our analysis is based on growth data of 21 patients with common 1.4/1.2 Mb microdeletions, including three patients with a Weaver-like appearance. Overgrowth was most evident in preschool children (2-6 years, n ¼ 10, P ¼ 0.02). We conclude that childhood overgrowth is part of the phenotypic spectrum in patients with the common 1.4/1.2 Mb NF1 microdeletions and assume that the chromosomal region comprised by the microdeletions contains a gene whose haploinsufficiency causes overgrowth.

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“…This hypothesis was confirmed only recently at the Segmental NF molecular level by fluorescence in situ hybridization which identified an NF1 microdeletion in a patient with segmental NF in whom the mutant NF1 allele was present in a mosaic pattern in cultured fibroblasts from a caf áe-au-lait macule, but was absent in fibroblasts from normal skin. 21) These findings proved that the molecular basis of segmental NF is a mutation in the NF1 gene, and that the regional distribution of manifestations reflects different cell clone lines. Mosaic localized NF1 is another term proposed for segmental NF which acknowledges that the pathogenesis is a postconceptional mutation occurring in somatic cells rather than in germ cells and leading to somatic mosaicism.…”

Section: Discussionmentioning

confidence: 80%

Giant Plexiform Neurofibroma and Suboccipital Meningocele Manifesting as Segmental Neurofibromatosis -Case Report-

Kurimoto

Mizumaki

Fukuda

et al. 2008

Neurol. Med. Chir.(Tokyo)

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Fig. 1 Photographs of the patient's shoulder demonstrating a giant nevus spilus (A) and numerous caf áe-au-lait spots on the right side of the neck (B). AbstractA 34-year-old woman presented with segmental neurofibromatosis manifesting as a soft lump with a large caf áe-au-lait macule on her occipital region and neck. Magnetic resonance imaging showed a thick skin tumor in the occipital region and posterior neck, and a suboccipital meningocele which seemed to have no association with her symptoms. Biopsy lead to a histological diagnosis of giant plexiform neurofibroma. During biopsy, massive local bleeding occurred and hemostasis was achieved by electrocautery and meticulous suture ligation. The postoperative course was uneventful and observation was continued for both the giant plexiform neurofibroma and the meningocele.

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Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene

Cited by 209 publications

References 19 publications

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept

Allelic loss underlies type 2 segmental Hailey-Hailey disease, providing molecular confirmation of a novel genetic concept

Childhood overgrowth in patients with common NF1 microdeletions

Giant Plexiform Neurofibroma and Suboccipital Meningocele Manifesting as Segmental Neurofibromatosis -Case Report-

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