四例13q33-q34缺失患者的临床表型与遗传学分析

Phenotypic and genetic analysis of four patients with 13q33-q34 microdeletion

目的探讨13q33-q34微缺失患儿基因组微缺失与临床表型的关系。方法应用常规G显带技术分析4例患儿外周血染色体，应用比较基因组杂交芯片和单核苷酸多态性芯片检测患儿的微小基因组拷贝数改变。结果常规染色体核型分析显示例1核型为46，XY，9qh＋，13qs；例2核型为46，XX，der（13）；例3核型为46，XX，r（13）（p11．2q32）[433／45，XX，-13[41146，XX，r（13；13）[21147，XX，2r（13；13）[1]；例4未进行染色体检查。芯片分析结果显示4例患儿在染色体13q33-q34区域存在不同程度的微缺失，且均表现出13q33-q34缺失的智力低下、面部特殊、小头畸形、肌张力低下、较低的出生体重或生殖器异常等常见特征。结论患儿表型的严重程度与13q33-q34缺失片段大小缺乏直接的关联，低比例的患者具有先天性心脏病，表明心脏疾病具有复杂的发病机制。13q33-q34区域内的EFNB2、LIG4和SOX1基因可能是智力落后的候选基因，LIG4还可能是小头畸形的候选基因。

Objective To explore the correlation between 13q33-q34 microdeletion and clinical phenotype. Methods Routine chromosomal banding was performed to analyze the karyotype, while array- based comparative genomic hybridization （aCGH array） and single nucleotide polymorphism array（SNP array） were employed to investigate the genome copy number variations. Results The karyotype of patient 1 was 46, XY, 9qh＋,13qs. Patient 2 showed 46, XX, der （13）. Patient 3 showed 46,XX,r（13） （pll. 2q32）[43]/45,XX,-13[4]/46, XX, r（13;13） [2]/47, XX, 2r（13; 13） [1]. Patient 4 did not undergo chromosome karyotyping analysis. Array analysis showed that four patients have different microdeletions in 13q33-34 region and had common features of 13q33-q34deletion including intellectual disability, facial dysmorphism, microcephaly, hypotonia, low birth weight and genital abnormality. Conclusion The severity of phenotypes showed no correlation with the size of deletion in 13q33-q34. The lower percentage of patients with congenital heart disease suggested a complex pathogenesis of such disease. EFNB2, LIG4 and SOX1 in 13q33-34 region are promising candidates for mental retardation. LIG4 was also a likely candidate for microcephaly.