Eur J Med Genet

Autor: Caroline Deiller, Hugues Loiseau, Thierry Fabre, Julie Tinat, Julien Van-Gils, Cécile Zordan, Béatrice Parfait, Cyril Goizet, Michel Vidaud, Claire Delleci, Joëlle Cohen
Přispěvatelé: Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: European Journal of Medical Genetics
European Journal of Medical Genetics, Elsevier, 2019, 62 (8), pp.103680. ⟨10.1016/j.ejmg.2019.103680⟩
ISSN: 1769-7212
DOI: 10.1016/j.ejmg.2019.103680⟩
Popis: Schwannomatosis is a rare affection predisposing to multiple peripheral neurologic tumors development. Approximatively, one third of patients with schwannomatosis are carriers of a germline mutation in LZTR1 (Leucin Zipper Transcription Regulator 1). Tumorigenesis in schwannomatosis responds to a somatic 5-hit/3-step mechanism resulting in a loss of function (LOF) of LZTR1 and the contiguous genes of locus 22q11.2q12.2. Effectively, LZTR1 is mapped on 22q11.2 and centromeric to SMARCB1 also implicated in the determinism of schwannomatosis and NF2, responsible for neurofibromatosis type 2. On a somatic point of view, LZTR1 mutations are known to drive with a significant frequency glioblastoma (GB) development. We report here two families in which segregate both multiple schwannomas and GB. In the first family, the proband received a diagnosis with of schwannomatosis after a surgery for a lumbar schwannoma at age 43, molecularly confirmed by identification of a germline heterozygous mutation in LZTR1. Her father, having unremarkable medical history deceased from an apparently isolated GB at age 59. In the second family, LZTR1-related schwannomatosis was diagnosed in the index case at age 70 after multiple schwannomas surgeries. Her elder sister had no neurological medical history before occurrence of a lethal GB at age 78. Molecular analysis of GB sample from both affected relatives showed the presence of the familial mutation. These observations hypothesize a potential link between schwannomatosis and the GB development.
Databáze: OpenAIRE
Externí odkaz: