Baser M E, Mautner V F, Ragge N K, Nechiporuk A, Riccardi V M, Klein J, Sainz J, Pulst S M
Division of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Neurology. 1996 Nov;47(5):1269-77. doi: 10.1212/wnl.47.5.1269.
Neurofibromatosis 2 (NF2) is an autosomal dominant disorder that causes nervous system tumors and ocular abnormalities such as early-onset lenticular opacities. We assessed the clinical spectrum of NF2 at the time of presymptomatic DNA diagnosis in at-risk first-degree relatives. We studied five multigeneration NF2 families with short tandem repeat markers near the NF2 gene (NF2); gadolinium-enhanced high-resolution magnetic resonance imaging (GE-MRI); and ocular, dermatologic, and neurologic examinations. Eleven of 31 asymptomatic at-risk first-degree relatives were predicted by segregation analysis to be NF2 mutation carriers. Nine of the 11 NF2 mutation carriers were clinically evaluated. Four mutation carriers, including a 7-year-old, had vestibular schwannomas, early-onset cataracts, or both. However, five mutation carriers did not have clinical abnormalities, including a 38-year-old with normal cranial and spinal GE-MRIs and a normal ocular examination. These results indicate that clinical abnormalities can be present in young, but absent in middle-aged, presymptomatic NF2 mutation carriers. By identifying presymptomatic NF2 mutation carriers, DNA diagnosis of NF2 can improve genetic counseling and clinical management, and possibly reduce psychosocial difficulties in at-risk individuals.
神经纤维瘤病2型（NF2）是一种常染色体显性疾病，可导致神经系统肿瘤和眼部异常，如早发性晶状体混浊。我们在有患病风险的一级亲属进行症状前DNA诊断时评估了NF2的临床谱。我们研究了五个多代NF2家系，采用NF2基因（NF2）附近的短串联重复序列标记、钆增强高分辨率磁共振成像（GE-MRI）以及眼科、皮肤科和神经科检查。通过分离分析预测，31名无症状的有患病风险一级亲属中有11名是NF2突变携带者。对这11名NF2突变携带者中的9名进行了临床评估。包括一名7岁儿童在内的4名突变携带者患有前庭神经鞘瘤、早发性白内障或两者皆有。然而，5名突变携带者没有临床异常，其中一名38岁的患者头颅和脊柱GE-MRI正常，眼科检查也正常。这些结果表明，症状前NF2突变携带者在年轻时可能出现临床异常，但在中年时可能没有。通过识别症状前NF2突变携带者，NF2的DNA诊断可以改善遗传咨询和临床管理，并可能减少有患病风险个体的心理社会困难。
