摘要
目的：明确一家系中两例智力低下患者的遗传学病因,并分析其与临床表型的关系。方法应用常规染色体 G 显带分析患者的核型,之后应用单核苷酸多态性(single nucleotide polymorphism,SNP)微阵列芯片检测潜在的染色体微缺失和微重复,同时采用荧光原位杂交(fluorescence in situ hybridization, FISH)验证芯片检测的结果。结果染色体核型分析表明先证者及其叔叔均正常。SNP 微阵列芯片分析表明先证者染色体16p13.3区存在1.147 Mb 的缺失,19q13.42-q13.43区存在2.948 Mb 的重复,分子核型为46,XY,16p13.3(85880-1233819)×1,19q13.42-13.43(56008597-58956816)×3。FISH 分析表明两例患者异常的16号染色体短臂末端均为19号染色体长臂末端。两例患者的父亲均为16p 和19q 末端隐匿平衡易位携带者。患者存在由 t(16；19)形成的 der(16)衍生染色体,导致16p 末端单体及19q 末端三体,该异常源自 t(16；19)平衡易位父亲生殖细胞形成时发生的染色体异常。先证者的主要表现包括智力低下、言语少、面容特殊(眼距稍宽、眼裂向下、鼻梁低、门牙外呲、缝隙大),其叔叔表型略轻,主要表现为智力低下。先证者父母表型均正常。结论此家系中两例患者均继承了来自父亲的一条衍生16号染色体,导致16p13.3微缺失和19q13.4微重复,二者可能是导致智力低下的原因。染色体末端同时存在缺失和重复往往提示亚端粒区重组,SNP 微阵列芯片分析结合 FISH 检测能够精确分析染色体的拷贝数变异,同时明确染色体结构异常的来源,有助于再发风险评估和产前诊断。
Abstract
Objective To determine the genetic cause for two mentally retarded patients from a family,and to correlate their genotypes with clinical phenotypes.Methods Routine G-banded karyotyping analysis was performed.Single nucleotide polymorphism (SNP)microarray analysis was used to detect microdeletions or microduplications.Fluorescence in situ hybridization (FISH)was used to ascertain the origin of chromosomal abnormalities.Results Both proband and his uncle showed a normal karyotype.SNP microarray analysis has identified a 1.147-Mb microdeletion at 1 6p13.3 (85 880-1 233 81 9)and a 2.948-Mb microduplication at 1 9q13.42-q13.43 (56 008 597-58 956 81 6).FISH analysis confirmed that the patient has inherited a derivative chromosome 1 6 from his father.The proband presented with mental retardation, reduced speech,and facial dysmorphism (hypertelorism,down-slanting palpebral fissure,low nasal bridge and wide gap between front teeth).His uncle presented with a milder phenotype with mental retardation. Conclusion Both the proband and his uncle have carried a chromosome microdeletion at 1 6p and microduplication at 1 9q,which were originated from their fathers carrying a balanced 1 6;1 9 translocation. Combined SNP microarray analysis and FISH assay are useful for the detection the copy number variations and delineation of potential structural changes,which may help with evaluation of recurrence risk for this family.
NETL
NSTL
维普
万方数据