Ruiz-Botero Felipe, Pachajoa Harry
Faculty of Health, Universidad Icesi, Research Centre on Congenital Anomalies and Rare Diseases (CIACER), Calle 18 No. 122-135, bloque L, Oficina: 5025A Pance, Cali, Colombia.
J Med Case Rep. 2016 Jul 27;10:204. doi: 10.1186/s13256-016-0988-2.
Genetic disorders are a major cause in the etiology of cases with intellectual disability; however, analysis by a conventional technique such as cytogenetic karyotyping only allows the detection of chromosomal alterations in approximately 9.5 % of cases. The inclusion of new technologies such as high resolution microarray analysis has allowed the study of alterations in chromosomal segments that are less than 5 Mb in length; this has led to an increase in the diagnosis of these patients of up to 25 %.
We report the first case of an 8-year-old Colombian girl of mixed race ancestry (Mestizo), with clinical features that include: delayed psychomotor and language development, intellectual disability, upward slanting palpebral fissures, divergent strabismus, low-set and rotated ears, tall and broad nasal bridge, flat philtrum, bifid uvula, posterior cleft palate, increased anteroposterior diameter of her chest, congenital heart defect type interventricular communication, scoliosis, and umbilical hernia. Genetic analysis was performed using comparative genomic hybridization array, which evidenced the deletion of a region of approximately 3.608 Mb on chromosome 21q22.3, and a duplication of 12.326 Mb on chromosome 7q35q36.3, these alterations affect approximately 112 and 186 genes, respectively.
To date, this is the first report of an associated terminal deletion of 21q and 7q duplication in a patient with delayed psychomotor development and intellectual disability. We consider that future implementation of exome and RNA sequencing techniques, and analysis of their proteomic expression in a clinical context could lead to better analysis and interpretation of the genotype-phenotype correlation in cases similar to that described.
遗传疾病是智力残疾病例病因中的主要因素；然而，采用常规技术如细胞遗传学核型分析仅能在约9.5%的病例中检测到染色体改变。纳入高分辨率微阵列分析等新技术使得对长度小于5 Mb的染色体片段改变的研究成为可能；这使得这些患者的诊断率提高了25%。
我们报告了首例具有混血（梅斯蒂索人）血统的8岁哥伦比亚女孩，其临床特征包括：精神运动和语言发育迟缓、智力残疾、睑裂向上倾斜、外斜视、耳朵低位且旋转、鼻梁高而宽、人中扁平、悬雍垂裂、腭裂、胸廓前后径增加、室间隔缺损型先天性心脏缺陷、脊柱侧弯和脐疝。使用比较基因组杂交阵列进行了基因分析，结果显示21号染色体q22.3区域缺失约3.608 Mb，7号染色体q35q36.3区域重复12.326 Mb，这些改变分别影响约112个和186个基因。
迄今为止，这是首例关于精神运动发育迟缓及智力残疾患者合并21号染色体末端缺失和7号染色体重复的报告。我们认为，未来在临床环境中实施外显子组和RNA测序技术及其蛋白质组表达分析，可能会对类似本文所述病例的基因型 - 表型相关性进行更好的分析和解释。
