耳鼻咽喉科・頭頸部外科94巻12号

2022年11月発行

特集 この1冊でわかる遺伝学的検査—基礎知識と臨床応用

《臨床への応用》

神経線維腫症2型（聴神経腫瘍）—臨床的・遺伝的背景の解析

著者： 中冨浩文¹

所属機関： ¹杏林大学医学部脳神経外科

ページ範囲：P.1028 - P.1031

文献概要

POINT

●ターゲットディープシークエンスにより診断率が向上し，モザイク型神経線維腫症2型の非常に多様な表現型が明らかになった。

●ターゲットディープシークエンスによる遺伝子型-表現型相関に基づき，神経線維腫症2型患者における機能的な早期予後予測が可能となった。

●「truncating」「モザイク」「症状発現年齢≧25」は機能障害に最も大きな影響を与える。

参考文献

1）Evans DG：Neurofibromatosis type 2（NF2）：a clinical and molecular review. Orphanet J Rare Dis 4：16, 2009

2）Evans DG, et al：A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29：841-846, 1992

3）Smith MJ, et al：Revisiting neurofibromatosis type 2 diagnostic criteria to exclude LZTR1-related schwannomatosis. Neurology 88：87-92, 2017

4）Rouleau GA, et al：Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363：515-521, 1993

5）Evans DG, et al：Mosaicism in neurofibromatosis type 2：an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification. J Med Genet 44：424-428, 2007

6）Kluwe L, et al：Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 40：109-114, 2003

7）Louvrier C, et al：Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis. Neuro Oncol 20：917-929, 2018

8）Evans DG, et al；English Specialist NF2 Research Group：Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing. Genet Med 21：1525-1533, 2019

9）Evans DG, et al；English Specialist NF research group：Incidence of mosaicism in 1055 de novo NF2 cases：much higher than previous estimates with high utility of next-generation sequencing. Genet Med 22：53-59, 2020

10）D'Gama AM, et al：Somatic mosaicism and neurodevelopmental disease. Nat Neurosci 21：1504-1514, 2018

11）Tyburczy ME, et al：Mosaic and intronic mutations in TSC1/TSC2 explain the majority of TSC patients with no mutation identified by conventional testing. PLoS Genet 11：e1005637, 2015

12）Teranishi Y, et al：Targeted deep sequencing of DNA from multiple tissue types improves the diagnostic rate and reveals a highly diverse phenotype of mosaic neurofibromatosis type 2. J Med Genet 58：701-711, 2021

13）Asthagiri AR, et al：Neurofibromatosis type 2. Lancet 373：1974-1986, 2009

［Internet］. University of Washington, Seattle, 1993

15）Teranishi Y, et al：Early prediction of functional prognosis in neurofibromatosis type 2 patients based on genotype-phenotype correlation with targeted deep sequencing. Sci Rep 12：9543, 2022