A girl with neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17
A girl with neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17
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DOI：
10.1002/ajmg.a.31569
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发表时间：
2007-01-01
影响因子：
2
通讯作者：
Sedlacek, Zdenek
中科院分区：
文献类型：
--
作者：
Havlovicova, Marketa;Novotna, Drahuse;Sedlacek, Zdenek
我们描述了一个患有1型神经纤维瘤病(NF1)的女孩，有轻度畸形特征，生长发育迟缓和智力低下，自闭症，以及17号环状染色体和17号染色体单体的嵌合体。用经典细胞遗传学、荧光原位杂交(FISH)和多重连接依赖的探针扩增(MLPA)相结合的方法，确定了17p的遗传物质缺失的程度为0.6-2.5Mb，17q的遗传物质缺失的程度约为10Mb。根据我们的观察和对文献的回顾，我们认为，除了普遍存在的基于环不稳定的、对所涉及的染色体不太特异的“环综合征”外，各种环染色体还具有各自独特的表型。我们认为在我们的患者中，导致NF1诊断的症状可能归因于她的一些体细胞中NF1基因的嵌合性。类似的机制或各自的疾病基因直接参与这种异常可能也会影响自闭症和其他症状的发展。我们提出了一个问题，如果从体细胞的实质性部分丢失17号染色体的一个副本，是否也会对患者未来的风险产生特定的后果，例如，由于BRCA1和TP53基因的嵌合性。(C)2006年Wiley-Liss，Inc.
We describe a girl with neurofibromatosis type 1 (NF1), mild dysmorphic features, growth and mental retardation, autism, and mosaicism of ring chromosome 17 and chromosome 17 monosomy. The extent of genetic material deleted from the ring chromosome was determined using a combination of classical cytogenetics, fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) to be 0.6-2.5 Mb on 17p, and up to about 10 Mb on 17q. Based on our observations and on a review of the literature we argue that in addition to a universal "ring syndrome" which is based on ring instability and is less specific for the chromosome involved, various ring chromosomes underlie their own characteristic phenotypes. We propose that the symptoms leading to the diagnosis of NF1 in our patient could be attributed to mosaic hemizygosity for the NF1 gene in some of her somatic cells. A similar mechanism or a direct involvement of respective disease genes in the aberration could possibly influence also the development of autism and other symptoms. We raise a question if the loss of one copy of chromosome 17 from a substantisal fraction of somatic cells can have specific consequences also for future risks of the patient, for example, due to the mosaic hemizygosity for the BRCA1 and TP53 genes. (c) 2006 Wiley-Liss, Inc.