Kluwe Lan, Siebert Reiner, Gesk Stefan, Friedrich Reinhard E, Tinschert Sigrid, Kehrer-Sawatzki Hildegard, Mautner Victor-F
Laboratory for Tumor Biology and Development Disorders, Department of Maxillofacial Surgery, University Hospital Hamburg-Eppendorf; Hamburg, Germany.
Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Kiel,Germany.
Hum Mutat. 2004 Feb;23(2):111-116. doi: 10.1002/humu.10299.
A total of 500 unselected unrelated neurofibromatosis 1 (NF1) patients were screened for deletions of the NF1 gene. After excluding 67 patients with known intragenic NF1 mutations, the remaining 433 were genotyped using six intragenic and one distal microsatellite marker for the NF1 gene. A total of 28 patients were hemi- or homozygous for all seven markers and were thus considered as candidates for NF1 deletion with a calculated probability of 99.99%. Metaphase or interphase cells were available from 23 of these 28 individuals for molecular cytogenetics. Fluorescence in situ hybridization (FISH) confirmed an NF1 deletion in 22 (96%) of the 23 patients. Thus, a constitutional deletion of the NF1 gene is responsible for the disease phenotype in at least 4.4% of the 500 unselected NF1 patients. Genotyping using multiple microsatellite markers may provide a simple, inexpensive, and efficient strategy for screening deletions of the NF1 gene, and can as well be applied for other large genes.
总共对500例未经选择的散发性神经纤维瘤病1型（NF1）患者进行了NF1基因缺失筛查。在排除67例已知基因内NF1突变的患者后，对其余433例患者使用6个基因内微卫星标记和1个NF1基因远端微卫星标记进行基因分型。共有28例患者在所有7个标记上呈半合子或纯合子状态，因此被视为NF1基因缺失的候选者，计算得出的概率为99.99%。这28例个体中有23例可获得中期或间期细胞用于分子细胞遗传学分析。荧光原位杂交（FISH）证实23例患者中有22例（96%）存在NF1基因缺失。因此，在这500例未经选择的NF1患者中，至少4.4%的患者疾病表型由NF1基因的先天性缺失所致。使用多个微卫星标记进行基因分型可为筛查NF1基因缺失提供一种简单、廉价且高效的策略，并且也可应用于其他大基因。
