The Children's Hospital, Section of Clinical Genetics and Metabolism, Denver, UC Denver, Aurora, CO, USA.
Eur J Hum Genet. 2011 Jan;19(1):43-9. doi: 10.1038/ejhg.2010.121. Epub 2010 Aug 18.
We demonstrate the utility of an exon coverage microarray platform in detecting intragenic deletions: one in exons 24-27 of the EP300 gene and another in exons 27 and 28 of the CREBBP gene in two patients with Rubinstein-Taybi syndrome (RSTS). RSTS is a heterogeneous disorder in which approximately 45-55% of cases result from deletion or mutations in the CREBBP gene and an unknown portion of cases result from gene changes in EP300. The first case is a 3-year-old female with an exonic deletion of the EP300 gene who has classic facial features of RSTS without the thumb and great toe anomalies, consistent with the milder skeletal phenotype that has been described in other RSTS cases with EP300 mutations. In addition, the mother of this patient also had preeclampsia during pregnancy, which has been infrequently reported. The second case is a newborn male who has the classical features of RSTS. Our results illustrate that exon-targeted array comparative genomic hybridization (aCGH) is a powerful tool for detecting clinically significant intragenic rearrangements that would be otherwise missed by aCGH platforms lacking sufficient exonic coverage or sequencing of the gene of interest.
在两名 Rubinstein-Taybi 综合征（RSTS）患者中，一个位于 EP300 基因的外显子 24-27 中，另一个位于 CREBBP 基因的外显子 27 和 28 中。RSTS 是一种异质性疾病，大约 45-55%的病例是由于 CREBBP 基因的缺失或突变引起的，而未知部分的病例是由于 EP300 基因的变化引起的。第一个病例是一名 3 岁女性，存在 EP300 基因的外显子缺失，具有 RSTS 的典型面部特征，但没有拇指和大脚趾异常，与其他 EP300 突变的 RSTS 病例中描述的较轻的骨骼表型一致。此外，该患者的母亲在怀孕期间也患有子痫前期，这很少有报道。第二个病例是一名新生儿男性，具有典型的 RSTS 特征。我们的结果表明，外显子靶向的阵列比较基因组杂交（aCGH）是一种强大的工具，可以检测临床上有意义的基因内重排，如果缺乏足够的外显子覆盖或感兴趣基因的测序，aCGH 平台可能会错过这些重排。
