Wu C L, Thakker N, Neary W, Black G, Lye R, Ramsden R T, Read A P, Evans D G
University Department of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester, UK.
J Med Genet. 1998 Dec;35(12):973-7. doi: 10.1136/jmg.35.12.973.
Patients who present with unilateral vestibular schwannomas either at a young age or with additional features of type 2 neurofibromatosis (NF2) are at risk of developing bilateral disease and transmitting a risk of neurogenic tumours to their offspring. We have identified 15 patients from a series of 537 with unilateral vestibular schwannomas who also had one or more of the following: other tumours (10/15), features of NF2 (3/15), or a family history of neurogenic tumours (5/15). No germline NF2 mutations were detected and in 7/9 cases where tumour material was available for analysis a germline mutation in the NF2 gene has been excluded. Although a possibility of gonosomal mosaicism still exists, exclusion tests for the offspring are now possible. We suggest a general strategy, based on analysis of tumour DNA, for distinguishing sporadic and familial cases of tumours caused by two hit mechanisms. Application of this strategy suggests that most instances of unilateral vestibular schwannoma which do not fulfil criteria for NF2 represent chance occurrences.
患有单侧前庭神经鞘瘤的患者，若发病年龄较轻或伴有2型神经纤维瘤病（NF2）的其他特征，则有发生双侧疾病的风险，并将神经源性肿瘤的风险遗传给后代。我们从537例单侧前庭神经鞘瘤患者中识别出15例，这些患者还具有以下一种或多种情况：其他肿瘤（10/15）、NF2特征（3/15）或神经源性肿瘤家族史（5/15）。未检测到种系NF2突变，在9例可获得肿瘤材料进行分析的病例中，有7例排除了NF2基因的种系突变。尽管仍存在性染色体镶嵌现象的可能性，但现在可以对后代进行排除检测。我们基于肿瘤DNA分析提出了一种通用策略，用于区分由双打击机制引起的肿瘤的散发性和家族性病例。应用该策略表明，大多数不符合NF2标准的单侧前庭神经鞘瘤病例属于偶发情况。
