Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb

BMC Medical Genomics
Elisabeth CastellanosNF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC

Abstract

A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inac...Continue Reading

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Citations

Dec 27, 2015·Seminars in Pediatric Neurology·Martino Ruggieri, Andrea D Praticò
Dec 27, 2015·Seminars in Pediatric Neurology·Martino RuggieriDafydd Gareth Evans
Nov 28, 2017·Annual Review of Genetics·Young H LimKeith A Choate
Jan 13, 2018·JAMA Dermatology·Elisabeth CastellanosUNKNOWN for CSUR Phakomatoses Multidisciplinary Clinics HUGTiP-ICO-IGTP
Dec 19, 2019·Journal of Child Neurology·Grant L HomManikum Moodley
Apr 4, 2017·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Rosario CaltabianoMartino Ruggieri

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Methods Mentioned

BETA
PCR

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