MacCollin M, Braverman N, Viskochil D, Ruttledge M, Davis K, Ojemann R, Gusella J, Parry D M
Department of Neurology, Massachusetts General Hospital, Boston, USA.
Ann Neurol. 1996 Sep;40(3):440-5. doi: 10.1002/ana.410400313.
Neurofibromatosis 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other nonmalignant tumors of the brain, spinal cord, and peripheral nerves. Although the average age of onset of NF2 is 20 years, some individuals may become symptomatic in childhood. We studied 5 unrelated NF2 patients who became symptomatic before age 13. All 5 had multiple tumors in addition to vestibular schwannoma, and none had a positive family history. Sequence analysis of the NF2 gene revealed identical nonsense mutation of exon 6 in 3 patients. Because this mutation destroys a restriction enzyme recognition site, genomic DNA from the 2 other children was directly tested for this change and identical alterations were detected. Although the work of our laboratory and others has not, in general, detected identical mutations in unrelated patients, this mutation seems to occur particularly frequently in the pediatric population and thus may be associated with an especially severe phenotype. Restriction analysis in children with NF2 may be a cost effective way of identifying their mutation. Further work is needed to characterize the effects of this change on the NF2 protein product and its relationship to this severe phenotype.
神经纤维瘤病2型（NF2）是一种常染色体显性疾病，其特征为双侧前庭神经鞘瘤以及脑、脊髓和周围神经的其他非恶性肿瘤。虽然NF2的平均发病年龄为20岁，但一些个体在儿童期就可能出现症状。我们研究了5例在13岁之前出现症状的无亲缘关系的NF2患者。所有5例除前庭神经鞘瘤外均有多个肿瘤，且均无阳性家族史。对NF2基因的序列分析显示，3例患者的第6外显子存在相同的无义突变。由于该突变破坏了一个限制性酶识别位点，因此对另外2名儿童的基因组DNA直接检测了这一变化，并检测到相同的改变。虽然我们实验室及其他机构的工作总体上未在无亲缘关系的患者中检测到相同的突变，但这种突变似乎在儿童人群中特别常见，因此可能与特别严重的表型相关。对NF2患儿进行限制性分析可能是一种经济有效的识别其突变的方法。需要进一步开展工作来明确这一变化对NF2蛋白产物的影响及其与这种严重表型的关系。
