一例发育落后合并多发先天畸形患儿9q和22q亚端粒不平衡重组

Unbalanced subtelomic rearrangement involving 9q and 22q in a child with mental retardation and multiple congenital anomalies

目的鉴定1例发育落后合并多发先天异常患儿的遗传学病因。方法应用常规G显带技术分析患儿及其父母外周血染色体，然后应用比较基因组杂交芯片技术（arraycomparativegenomichybridization，arrayCGH）进一步检测患儿微小染色体改变。荧光原位杂交（fluorescenceinsituhybridization，FIsH）验证芯片检测结果。结果常规染色体检查结果显示患儿及其父母未发现明显染色体异常。ArrayCGH分析发现患儿区域2．8Mb片段缺失，22q13．2q13．33区域8．1Mb片段重复。FISH结果显示患儿异常9号染色体长臂末端为22号长臂末端；母亲22号与9号染色体末端发生相互易位。父亲9号染色体和22号染色体信号正常。FISH结果表明患儿存在由t（9；22）形成的der（9）衍生染色体，导致9q末端单体及22q末端三体，该异常源自t（9；22）平衡易位母亲生殖细胞形成中出现的染色体异常。患儿临床表现包括发育落后，面容特殊及多发畸形。母亲再次妊娠，FISH结果显示胎儿脐血9号染色体和22号染色体信号正常，出生后随访发育正常。结论本例患儿异常表型由9q末端单体及22q末端三体导致。染色体末端同时存在缺失和重复往往提示亚端粒区域重组，array-CGH结合荧光原位杂交技术可以帮助发现和确认亚端粒重组，并为诊断明确的家庭提供再发风险评估和产前诊断。

Objective To determine genetic cause for a patient with development delay and multiple congenital anomalies. Methods Routine karyotype analysis was performed for the patient and his parents. Array comparative genomic hybridization （array CGH） was performed for the patient to detect cryptic chromosome aberration. Results Karyotype analysis revealed no obvious anomaly for the patient and his parents. Array CGH has detected a 2.8 Mb heterozygous deletion at 9q34.3 and an 8. 1 Mb heterozygous duplication at 22q. Fluorescence in situ hybridization analysis of the patient revealed an unbalanced subtelomeric translocation 46 ,XY,der（9）t（9 ; 22） （q34.3 ; q13.2q13.33） mat, which has resulted in partial trisomy 22q and partial monosomy 9q. Clinical features of the patient included developmental delay, facial dysmorphism and multiple congenital anomalies. Upon subsequent pregnancy, FISH analysis revealed that the fetus has inherited the normal chromosomes 9 and 22 from his mother. Postnatal follow-up confirmed normal development milestone and physiques in the child. Conclusion An unbalanced translocation involving 9q and 22q has been found in a child featuring multiple congenital anomalies, which is due to a balanced translocation 9; 22 in his mother. Array CGH and FISH have also helped with discovery of subtelomeric rearrangement. Prenatal diagnosis of this aberration in subsequent pregnancies with FISH can prevent the recurrence of this disease.