NF1 Microdeletions in Neurofibromatosis Type 1: From Genotype to Phenotype
NF1 Microdeletions in Neurofibromatosis Type 1: From Genotype to Phenotype
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DOI：
10.1002/humu.21271
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发表时间：
2010-06-01
期刊：
影响因子：
3.9
通讯作者：
Vidaud, Dominique
中科院分区：
文献类型：
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作者：
Pasmant, Eric;Sabbagh, Audrey;Vidaud, Dominique
在5-10%的患者中，1型神经纤维瘤病（NF1）是由包含整个NF1基因和可变数量的侧翼基因的微缺失引起的。在大多数病例中发现了两种复发性微缺失类型，微缺失断点位于NF1两侧的旁系区域（1.4 Mb 1型微缺失的近端NF1- rep -a和远端NF1- rep -c，以及1.2 Mb 2型微缺失的SUZ12和SUZ12P）。与基因内突变患者相比，NF1微缺失患者通常具有更严重的表型。我们使用高分辨率NF1定制阵列比较基因组杂交（CGH）对70名不相关的NF1微缺失患者的NF1微缺失进行了表征。在58例微缺失患者中研究了基因型-表型相关性，并与389例基因内截断NF1突变患者进行了比较，并以相同的标准化方式进行了表型分析。我们的研究结果无偏倚地证实，与基因内NF1突变的患者相比，微缺失患者存在一种连续基因综合征，其学习障碍和面部畸形的发生率显著高于基因内NF1突变的患者。微缺失NF1患者在儿童期过度生长中也表现出显著的趋势。高分辨率阵列- cgh发现了一种类似1.0 Mb微缺失类型的新复发，称为3型，断点位于NF1-REP-b中部和NF1-REP-c远端。(C) 2010 Wiley-Liss, Inc。
In 5-10% of patients, neurofibromatosis type 1 (NF1) results from microdeletions that encompass the entire NF1 gene and a variable number of flanking genes. Two recurrent microdeletion types are found in most cases, with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP-c for the 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type-2 microdeletion). A more severe phenotype is usually associated with NF1 microdeletion patients than in those with intragenic mutations. We characterized NF1 microdeletions in 70 unrelated NF1 microdeleted patients using a high-resolution NF1 custom array comparative genomic hybridization (CGH). Genotype-phenotype correlations were studied in 58 of these microdeletion patients and compared to 389 patients with intragenic truncating NF1 mutations and phenotyped in the same standardized way. Our results confirmed in an unbiased manner the existence of a contiguous gene syndrome with a significantly higher incidence of learning disabilities and facial dysmorphism in microdeleted patients compared to patients with intragenic NF1 mutations. Microdeleted NF1 patients also showed a trend toward significance for childhood overgrowth. High-resolution array-CGH identified a new recurrent similar to 1.0 Mb microdeletion type, designated as type-3, with breakpoints in the paralogous regions middle NF1-REP-b and distal NF1-REP-c. (C) 2010 Wiley-Liss, Inc.