A common set of at least 11 functional genes is lost in the majority of NF1 patients with gross deletions

被引:31
作者
Jenne, DE
Tinschert, S
Stegmann, E
Reimann, H
Nürnberg, P
Horn, D
Naumann, I
Buske, A
Thiel, G
机构
[1] Max Planck Inst Neurobiol, Dept Neuroimmunol, D-82152 Martinsried, Germany
[2] Humboldt Univ, Charite, Inst Med Genet, D-10098 Berlin, Germany
[3] Humboldt Univ, Charite, Inst Human Genet, D-13353 Berlin, Germany
关键词
D O I
10.1006/geno.2000.6179
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Large deletions of the NE1 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 BAG/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. (C) 2000 Academic Press.
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页码:93 / 97
页数:5
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