一例15号额外标记染色体致智力障碍、难治性癫癎伴中枢性性早熟患者的临床及遗传学分析

A clinical and genetic analysis of a child with supernumerary marker chromosome 15-caused mental retardation, intractable epilepsy, and central precocious puberty

摘要:

15号额外标记染色体是一种罕见的染色体异常，本文报道1例15号额外标记染色体患儿，就其临床诊治经过及遗传缺陷进行研究。患儿，女，9岁半，自幼智力、运动发育落后，7岁出现乳房发育，8岁半出现癫癎发作：发作形式多样，多种抗癫癎药物控制欠佳，头颅磁共振未见异常，脑电图提示癎样放电频繁。采用G显带核型分析、荧光原位杂交（FISH）、甲基化多重连接依赖性探针扩增技术（甲基化MLPA）和微阵列比较基因组杂交（array-CGH）等多种遗传学检测手段，明确患儿存在新生的15q重复：15q11-13区域母源性拷贝数复制增加，基因组重排的形式为47，XX，+inv dup （15）（pter→q13：q13→pter）。15q11-13区域拷贝数复制增加与智力障碍、难治性癫癎伴中枢性性早熟临床表现密切相关。建议对于不明原因智力障碍伴癫癎患儿进行高分辨染色体核型分析。

Abstract:

Supernumerary marker chromosome 15 is a rare chromosome abnormality. This paper reports the clinical diagnosis and treatment, as well as genetic defects, of a child with supernumerary marker chromosome 15. The patient was a 9.5-year-old girl who had mental and motor retardation since infancy, breast development at the age of 7 years, and seizures at the age of 8.5 years. Seizures occurred with various features and could not be controlled by a variety of antiepileptic drugs. No abnormalities were found by brain magnetic resonance imaging. Electroencephalogram showed frequent epileptiform discharges. G-banding karyotype analysis, fluorescence in situ hybridization, methylation-specific multiplex ligation-dependent probe amplification, and array comparative genomic hybridization identified a de novo 15q duplication in the patient. The maternal copy number increased in the 15q11-13 region. The form of genome rearrangement was 47,XX,+inv dup(15)(pter to q13:q13 to pter). The increased copy number in the 15q11-13 region is closely related to mental retardation, intractable epilepsy, and central precocious puberty. High-resolution karyotype analysis is recommended for children with unexplained mental retardation and epilepsy.