Baser M E, Ragge N K, Riccardi V M, Janus T, Gantz B, Pulst S M
Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, USA.
Am J Med Genet. 1996 Sep 6;64(4):563-7. doi: 10.1002/(SICI)1096-8628(19960906)64:4<563::AID-AJMG7>3.0.CO;2-Q.
Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affected organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes.
位于22q12染色体上的神经纤维瘤病2型（NF2）肿瘤抑制基因突变会导致一种临床症状多样的常染色体显性综合征，其特征为双侧前庭神经鞘瘤（VSs）、其他神经系统肿瘤以及早发性晶状体混浊。我们研究了三对患有NF2的同卵双胞胎（MZ），他们均患有双侧VSs，以区分临床症状差异的遗传因素和非遗传因素。评估包括头部和脊柱的钆增强高分辨率磁共振成像、裂隙灯神经眼科检查、体格检查以及使用微卫星标记进行的同卵性检测。每对MZ双胞胎在一般表型亚型（轻度或重度）方面通常一致，并且在受影响的器官系统方面也常常一致。然而，MZ双胞胎在疾病表现或进展的某些特征上存在不一致。例如，所有三对双胞胎在相关颅部肿瘤的存在或类型上均不一致。我们推测，NF2 MZ双胞胎之间的表型差异至少部分是由于随机过程，例如第二个NF2等位基因或其他基因等位基因的缺失。
