Coexistence of schwannomatosis and glioblastoma in two families.
European Journal of Medical Genetics. 2019-08-01; 62(8): 103680
DOI: 10.1016/j.ejmg.2019.103680
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1. Eur J Med Genet. 2019 Aug;62(8):103680. doi: 10.1016/j.ejmg.2019.103680. Epub
2019 May 22.
Coexistence of schwannomatosis and glioblastoma in two families.
Deiller C(1), Van-Gils J(2), Zordan C(1), Tinat J(1), Loiseau H(3), Fabre T(4),
Delleci C(5), Cohen J(6), Vidaud M(7), Parfait B(7), Goizet C(8).
Author information:
(1)CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France.
(2)CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France; Laboratoire
MRGM, INSERM U1211, Univ. Bordeaux, Bordeaux, France. Electronic address:
.
(3)CHU Bordeaux, Service de Neurochirurgie, Bordeaux, France.
(4)CHU Bordeaux, Service d’orthopédie, Bordeaux, France.
(5)CHU Bordeaux, Service de Médecine Physique et Réadaptation, Bordeaux, France.
(6)Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Assistance
Publique-Hôpitaux de Paris, Paris, France.
(7)Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Assistance
Publique-Hôpitaux de Paris, Paris, France; UMR INSERM 1016, Institut Cochin,
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
(8)CHU Bordeaux, Service de Génétique Médicale, Bordeaux, France; Laboratoire
MRGM, INSERM U1211, Univ. Bordeaux, Bordeaux, France.
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.
Published by Elsevier Masson SAS.
DOI: 10.1016/j.ejmg.2019.103680
PMID: 31128261 [Indexed for MEDLINE]