Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene.
Novel alleles, hemizygosity and deletions at an Alu-repeat within the neurofibromatosis type 1 (NF1) gene.
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1 型神经纤维瘤病 (NF1) 基因内 Alu 重复的新等位基因、半合性和缺失。
DOI：
10.1093/hmg/2.6.725
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发表时间：
1993
影响因子：
3.5
通讯作者：
X. Estivill
中科院分区：
文献类型：
--
作者：
C. Lázaro;A. Gaona;A. Ravella;V. Volpini;T. Casals;J. Fuentes;X. Estivill
1型神经纤维瘤病（NF 1）（von Recklinghausen）是一种常见的常染色体显性遗传病，其特征是存在外周神经纤维瘤、咖啡色斑和虹膜Lisch结节。由于NF 1基因座的高突变率，预计大多数患者具有不同的突变，限制了分子分析和遗传咨询以鉴定每个患者或家族中的突变，或使用DNA多态性。我们分析了一个重复多态性序列（AAAT），位于NF 1基因的内含子27，在70 NF 1和40 CEPH家庭，我们已经发现了一些遗传和分子异常。在两个家庭中，NF 1个体在NF 1的内含子27的AAAT重复和/或CA重复处是半合子的，由于间质缺失，其包括NF 1基因的内含子27至外显子37。一个71-bp的缺失在Alu序列中检测到三个NF 1家族成员的非NF 1染色体。在一个NF 1家族和三个CEPH家族中发现了AAAT重复的新等位基因，每个等位基因的AAAT重复突变率为0.36%，这是微卫星位点检测到的最高突变率之一。
Neurofibromatosis type 1 (NF1) (von Recklinghausen) is a common autosomal dominant disorder, characterised by the presence of peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. Due to the high mutation rate at the NF1 locus, most patients are expected to have different mutations, limiting molecular analysis and genetic counseling to the identification of the mutation in each patient or family, or to the use of DNA polymorphisms. We have analysed an Alu-repeat polymorphic sequence (AAAT), located in intron 27 of the NF1 gene, in 70 NF1 and 40 CEPH families and we have detected several genetic and molecular abnormalities. In two families the NF1 individuals were hemizygous at the AAAT-repeat and/or at the CA-repeat of intron 27 of NF1, due to interstitial deletions, which include intron 27 to exon 37 of the NF1 gene. A 71-bp deletion at the Alu sequence was detected in non-NF1 chromosomes of members of three NF1 families. New alleles at the AAAT-repeat were found in one NF1 family and in three CEPH families giving a mutation rate for this AAAT-repeat of 0.36% per allele, which is one of the highest detected for a microsatellite locus.