摘要目的 明确1例发育落后、矮小合并多发先天异常患儿的遗传学病因,并分析基因型与临床表型的关系.方法 应用常规染色体G显带技术分析患者的核型后,单核苷酸多态性(single nucleotide polymorphism,SNP)微阵列芯片技术检测潜在的染色体微缺失或微重复,同时应用荧光原位杂交(fluorescence in situ hybridization,FISH)技术验证芯片检测结果.结果 常规G显带核型分析显示患儿的核型为46,XY,der(18);父母的核型结果正常.染色体芯片结果显示患儿的染色体存在18p11.32-pter(chr18:136 227-1 370 501,hg19)区域1.23 Mb缺失和18q21.1-qter (chr18:44 250 359-78 013 728,hg19)区域33.76 Mb重复.双色FISH检测结果显示患儿的1条正常18号染色体短臂末端为橙色信号,长臂末端为绿色信号,而另1条重组的18号染色体长臂和短臂末端均为绿色信号,提示为18p末端缺失/18q末端重复.患儿临床表现符合18p末端缺失和18q末端重复的一些共同特征,如精神发育迟滞和生长发育落后,同时表现18p末端缺失的一些典型表现,如漏斗胸,矮小、生长激素缺乏,对生长激素的治疗有效,身高明显提高.携带18p缺失/18q重复病例的临床表型具有明显异质性,从表型正常到严重均有报道,缺乏一致性改变.结论 同一条染色体两个末端同时存在缺失和重复往往提示存在臂间倒位重组;同时存在两条染色体片段异常的病例临床表现通常存在变异性,因此很难进行基因型-表型关联分析.

abstractsObjective To explore the genetic cause for a patient with intellectual disability,short stature and multiple congenital anomalies,and to correlate the result with clinical phenotypes.Methods Routine karyotyping analysis was carried out on GTG-banded metaphase chromosomes.Single nucleotide polymorphism (SNP) microarray was used to detect microdeletions or microduplications in the patient.Fluorescence in situ hybridization (FISH) was used to ascertain the origin of aberrant chromosomes.Results The karyotype of the patient was 46,XY,der(18),while both of his parents had a normal karyotype.SNP array identified a 1.23 Mb deletion at 18p11.32-pter (chr18:136 227-1 370 501,hg19) and a 33.76 Mb duplication at 18q21.1-qter (chr18:44 250 359-78 013 728,hg19) in the patient.Above finding was confirmed by dual-color FISH with one color for 18p and another for 18q.The patient presented with some common features of 18p deletion and 18q duplication including intellectual disability and growth retardation,in addition with some features of 18p deletion including pectus excavatum,short stature and growth hormone (GH) deficiency.The patient showed progressive improvement of stature with GH therapy.Comparison of patients with previously reported dup(18q) +del(18p) recombinations suggested that,even for patients with similar breakpoints,their phenotypes have ranged from normal to severe and there were no consistent findings.Conclusion As aberrations involving double chromosomal segments often result in phenotypic variability,it has been difficult to correlate the genotype of our patient with his phenotype.