Kluwe L, Mautner V, Parry D M, Jacoby L B, Baser M, Gusella J, Davis K, Stavrou D, MacCollin M
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany.
Neurogenetics. 2000 Sep;3(1):17-24. doi: 10.1007/s100480000088.
Neurofibromatosis 2 (NF2) is an autosomal dominant disorder characterized by schwannomas and meningiomas that develop after inactivation of both copies of the NF2 gene. Approximately half of all patients with NF2 have unaffected parents and the disease results from new mutations at the NF2 locus. Loss of heterozygosity (LOH) in tumor specimens due to deletions covering the normal NF2 allele can be used to infer the haplotypes surrounding underlying mutations and determine the allelic origin of new mutations. We studied 71 sporadic NF2 patients using both LOH and pedigree analysis and compared the parental origin of the new mutation with the underlying molecular change. In the 45 informative individuals, 31 mutations (69%) were of paternal and 14 (31%) were of maternal origin (P=0.016). Comparison with corresponding constitutional mutations revealed no correlation between parental origin and the type or location of the mutations. However, in 4 of 6 patients with somatic mosaicism the NF2 mutation was of maternal origin. A slight parent of origin effect on severity of disease was found. Further clinical and molecular studies are needed to determine the basis of these unexpected observations.
神经纤维瘤病2型（NF2）是一种常染色体显性疾病，其特征为在NF2基因的两个拷贝均失活后出现的施万细胞瘤和脑膜瘤。所有NF2患者中约有一半的父母未受影响，该病是由NF2基因座的新突变引起的。由于覆盖正常NF2等位基因的缺失导致肿瘤标本中的杂合性缺失（LOH），可用于推断潜在突变周围的单倍型，并确定新突变的等位基因起源。我们使用LOH和系谱分析研究了71例散发性NF2患者，并将新突变的亲本起源与潜在的分子变化进行了比较。在45例信息充足的个体中，31个突变（69%）来自父系，14个（31%）来自母系（P=0.016）。与相应的胚系突变比较发现，亲本起源与突变的类型或位置之间没有相关性。然而，在6例体细胞镶嵌现象患者中的4例中，NF2突变来自母系。发现亲本起源对疾病严重程度有轻微影响。需要进一步的临床和分子研究来确定这些意外观察结果的基础。
