Mautner V F, Baser M E, Kluwe L
Neurological Department, Allgemeines Krankenhaus Ochsenzoll, Hamburg, Germany.
Hum Genet. 1996 Aug;98(2):203-6. doi: 10.1007/s004390050191.
Neurofibromatosis 2 (NF2) is a clinically variable autosomal dominant disorder, caused by mutations in the NF2 tumor suppressor gene on chromosome 22q12, that predisposes to nervous system tumors and ocular abnormalities. To assess intrafamilial phenotypic variability, we performed mutation analysis and clinical assessment on two multigeneration NF2 families with five patients and seven asymptomatic first-degree relatives of patients. One family had a point mutation of agCC --> ggCC at position 1447-2 at the exon 13/14 boundary predicted to lead to an altered splice acceptor sequence and exon deletion. The other family had an insertion of 2 base pairs (TC) at position 761 in exon 8, leading to a frameshift. Both mild and severe phenotypes occurred in each family, indicating that phenotypic variability in NF2 can be caused by factors other than NF2 mutations. Genetic counseling of NF2 families should include the possibility that presymptomatic NF2 mutation carriers can develop a different phenotype than previously diagnosed patients.
神经纤维瘤病2型（NF2）是一种临床症状多变的常染色体显性疾病，由位于22q12染色体上的NF2肿瘤抑制基因发生突变引起，易引发神经系统肿瘤和眼部异常。为评估家族内表型变异性，我们对两个有多代成员的NF2家族进行了突变分析和临床评估，其中一个家族有5名患者以及7名患者的无症状一级亲属。一个家族在第13/14外显子边界的1447-2位置发生了agCC --> ggCC的点突变，预计会导致剪接受体序列改变和外显子缺失。另一个家族在第8外显子的761位置插入了2个碱基对（TC），导致移码突变。两个家族中均出现了轻度和重度表型，这表明NF2的表型变异性可能由NF2突变以外的因素引起。对NF2家族进行遗传咨询时应考虑到，无症状的NF2突变携带者可能会出现与先前确诊患者不同的表型。
