Lopez Correa C, Brems H, Lázaro C, Estivill X, Clementi M, Mason S, Rutkowski J L, Marynen P, Legius E
Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Hum Mutat. 1999;14(5):387-93. doi: 10.1002/(SICI)1098-1004(199911)14:5<387::AID-HUMU4>3.0.CO;2-4.
Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized by a marked variability in expression. A more severe phenotype is frequently observed in the group of patients carrying a large NF1 deletion. To study the extent of the microdeletion in these NF1 patients, we generated a partial physical map of the NF1 flanking region. We describe seven PACs and three new polymorphic dinucleotide repeats located outside the NF1 gene and analyzed 20 unrelated individuals with an NF1 microdeletion in a collaborative study. We detected one individual with a substantially smaller deletion including only the NF1 gene and its three embedded genes. In the other 19 patients, the deletion extended at least 1 Mb. The parental origin of the deletion was determined in 15 individuals and was maternal in 13 and paternal in two cases. The new molecular tools described here can be used to unequivocally diagnose a possible extragenic extension of an NF1 deletion.
1型神经纤维瘤病（NF1）是一种常见的常染色体显性疾病，其特征是表达具有显著变异性。在携带大的NF1缺失的患者群体中，经常观察到更严重的表型。为了研究这些NF1患者中微缺失的程度，我们构建了NF1侧翼区域的部分物理图谱。我们描述了位于NF1基因外的7个P1人工染色体（PAC）和3个新的多态性二核苷酸重复序列，并在一项合作研究中分析了20名患有NF1微缺失的无关个体。我们检测到1名个体的缺失明显更小，仅包括NF1基因及其3个嵌入基因。在其他19名患者中，缺失至少延伸了1兆碱基（Mb）。在15名个体中确定了缺失的亲本来源，其中13例为母源，2例为父源。本文所述的新分子工具可用于明确诊断NF1缺失可能的基因外延伸。
