Rasmussen S A, Colman S D, Ho V T, Abernathy C R, Arn P H, Weiss L, Schwartz C, Saul R A, Wallace M R
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610-0296, USA.
J Med Genet. 1998 Jun;35(6):468-71. doi: 10.1136/jmg.35.6.468.
A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.
通过比较10个基因内多态性位点的患者和父母基因型，对一组1型神经纤维瘤病（NF1）患者进行了大的NF1基因缺失筛查。在67对患者/父母组合（47例新发突变患者和20例家族性病例）中，有5例（7.5%）表现出杂合性缺失（LOH），提示NF1基因缺失。与之前关于大的NF1缺失的报道相反，这5例患者没有严重的NF1表现、智力迟钝或畸形特征。所有5例缺失均为新发，且发生在母源染色体上。然而，2例患者表现出部分LOH，与该缺失的体细胞镶嵌现象一致，提示镶嵌现象在NF1中可能比之前认识到的更为常见（并且可能与临床严重程度有关）。我们认为，大的NF1缺失（1）并不总是与异常临床特征相关，（2）在母源等位基因上更易发生，（3）是NF1患者遗传性和体细胞突变的重要机制。
