A Synonymous Mutation in TCOF1 Causes Treacher Collins Syndrome Due to Mis-Splicing of a Constitutive Exon
A Synonymous Mutation in TCOF1 Causes Treacher Collins Syndrome Due to Mis-Splicing of a Constitutive Exon
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DOI：
10.1002/ajmg.a.32834
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发表时间：
2009-08-01
影响因子：
2
通讯作者：
Cutting, G. R.
中科院分区：
文献类型：
--
作者：
Macaya, D.;Katsanis, S. H.;Cutting, G. R.
解释疾病相关基因序列改变的致病性具有挑战性。这对于缺乏明显功能后果的新颖改变尤其如此。我们在此报告一例Treacher柯林斯综合征（TCS）患者，发现其携带一个先前报告的突变c.122 C> T，该突变预示p.A41 V，以及一个新的同义突变c.3612 A> C。家系分析显示c.122C > T突变在多个家系成员中与正常表型分离，而c.3612A > C突变在该患者中为新发突变。淋巴细胞中TCOF 1 RNA的分析显示转录本缺失外显子22。这些结果表明，患者的TCS是由于同义从头c.3612A > C突变引起的TCOF 1单倍不足。这项研究强调了临床和谱系评价在解释已知和新的序列改变中的重要性。(C)2009 Wiley-Liss，Inc.
Interpretation of the pathogenicity of sequence alterations in disease-associated genes is challenging. This is especially true for novel alterations that lack obvious functional consequences. We report here on a patient with Treacher Collins syndrome (TCS) found to carry a previously reported mutation, c.122C > T, which predicts p.A41V, and a novel synonymous mutation, c.3612A > C. Pedigree analysis showed that the c.122C > T mutation segregated with normal phenotypes in multiple family members while the c.3612A > C was de novo in the patient. Analysis of TCOF1 RNA in lymphocytes showed a transcript missing exon 22. These results show that TCS in the patient is due to haploinsufficiency of TCOF1 caused by the synonymous de novo c.3612A > C mutation. This study highlights the importance of clinical and pedigree evaluation in the interpretation of known and novel sequence alterations. (C) 2009 Wiley-Liss, Inc.