Jenne D E, Tinschert S, Stegmann E, Reimann H, Nürnberg P, Horn D, Naumann I, Buske A, Thiel G
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18A, Martinsried, 82152, Germany.
Genomics. 2000 May 15;66(1):93-7. doi: 10.1006/geno.2000.6179.
Large deletions of the NF1 locus occur in 5 to 10% of patients with neurofibromatosis and are commonly associated with specific additional abnormalities characterized by mental retardation, dysmorphic features, and intellectual impairment. To characterize the extent of codeleted genes we constructed a long-range physical BAC/PAC map around the NF1 locus between D17S117 and D17S57 and determined the deletion boundaries in seven unrelated patients. Surprisingly, the proximal and distal breakpoints in five of seven patients fall at almost identical positions, resulting in the loss of at least 11 functional genes. Five of six patients investigated showed a de novo deletion on the maternally derived chromosome. Since D17S117 and D17S57 were previously reported as the outer limits for the great majority of NF1 deletions, we suggest that most NF1 patients with deletion of the entire NF1 gene are hemizygous for the same set of at least 10 additional genes, including SHGC-37343, SHGC-2390, SHGC-34232, OMG, EVI2B, EVI2A, WI-9521, WI-6742, SHGC-34334, and KIAA0160, and thus present with a relatively uniform clinical phenotype.
5%至10%的神经纤维瘤病患者存在NF1基因座的大片段缺失，这些缺失通常与以智力发育迟缓、畸形特征和智力障碍为特征的特定额外异常相关。为了表征共缺失基因的范围，我们构建了一个围绕D17S117和D17S57之间NF1基因座的长程物理BAC/PAC图谱，并确定了7名无关患者的缺失边界。令人惊讶的是，7名患者中有5名的近端和远端断点几乎位于相同位置，导致至少11个功能基因缺失。在接受调查的6名患者中，有5名在母源染色体上出现了新生缺失。由于D17S117和D17S57先前被报道为绝大多数NF1缺失的外部界限，我们认为大多数缺失整个NF1基因的NF1患者对于同一组至少10个额外基因是半合子状态，这些基因包括SHGC - 37343、SHGC - 2390、SHGC - 34232、OMG、EVI2B、EVI2A、WI - 9521、WI - 6742、SHGC - 34334和KIAA0160，因此表现出相对一致的临床表型。
