一例新发21q22.12q22.13微缺失智力障碍患儿的分子遗传学研究

Identification of a de novo interstitial 21q22.12q22.13 deletion in a patient with intellectual disability

目的明确1例智力障碍、癫痫患儿分子遗传学病因,为该家系成员提供遗传咨询及产前诊断。方法应用染色体G显带核型分析、单核苷酸多态性微阵列及荧光实时定量PCR对患儿及家系成员进行遗传学检查。结果患儿外周血染色体核型显示为46,XX;单核苷酸多态性微阵列显示为arr[19]21q22.12q22.13(36 860 195~38 801 482)×1 dn,杂合缺失约1.9 Mb,包含DYRK1A、PIGP、HLCS、CLDN14四个致病基因;定量PCR检测结果显示:患儿DYRK1A基因第1外显子杂合缺失;父母及胎儿检测结果均未发现异常。结论应用单核苷酸多态性微阵列技术,明确了1例21q22微缺失患儿遗传学诊断,并为该家系成员提供了准确的产前诊断;为DYRK1A基因单倍体剂量不足可导致一种新的可被识别的综合征提供了新的依据;PIGP基因可能是导致早发性难治性癫痫的重要因素,但具体的致病机制仍需进一步的探究。

Objective To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy. Methods Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed. Results The karyotype of the child was determined as 46, XX;SNP array: arr[19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo. Conclusion A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.