目的探讨2例因“早发型胎儿生长受限”就诊的胎儿遗传学病因与表型之间的关联。方法收集2例胎儿的临床资料并进行羊水细胞的核型分析和染色体微阵列分析,后续抽取父母外周血确认纯合区域的来源。对其中1例病例胎盘的3处位点取样后进行...目的探讨2例因“早发型胎儿生长受限”就诊的胎儿遗传学病因与表型之间的关联。方法收集2例胎儿的临床资料并进行羊水细胞的核型分析和染色体微阵列分析,后续抽取父母外周血确认纯合区域的来源。对其中1例病例胎盘的3处位点取样后进行荧光原位杂交分析,推测单亲二体的可能发生机制。结果2例胎儿羊水细胞的染色体核型结果均正常,微阵列分析结果提示存在16号染色体末端的纯合区域(regions of homozygosity,ROH),长度分别为6.97Mb(位于16p13.3)和16.42Mb(位于16q22.3q24.3)。经过父母和胎儿的snp位点进行分析,确定这2例胎儿为单亲同二体和单亲异二体的混合型母源16号染色体单亲二体[uniparental disomy 16,UPD(16)]。最后对其中1例胎儿胎盘3个部位取材样本的荧光原位杂交(fluorescent in situ hybridization,FISH)结果显示,胎盘绒毛细胞中16号染色体三体比例占95%以上,证实为限制性胎盘嵌合体。结论母源性16号染色体单亲二体和胎儿生长受限表型的直接关联仍需要深入研究,该表型可能是由于胎盘限制性嵌合三体所引起,我们的结果为理解16号染色体单亲二体对胎儿和胎盘的临床效应提供了新数据。展开更多
Objective: Paternal deletion and maternal uniparental disomy are the principa l genetic subtypes associated with Prader- Willi syndrome (PWS). Recent clinica l findings suggest differences in phenotype between these s...Objective: Paternal deletion and maternal uniparental disomy are the principa l genetic subtypes associated with Prader- Willi syndrome (PWS). Recent clinica l findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho- physiological setup. Methods: Behaviour and event- related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT- AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT- AX task were r eaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality- specific inhibition and late gene ral inhibition, respectively. Results: The disomy group had fewer correct scores and increased reaction times as compared to the CPT- AX task than the control and deletion group. Both PWS subgroups differed significantly from the control g roup for the N200 amplitude. Only the control group showed the typical task modu lation for the N200 amplitude. The amplitude of the P300 component was considera bly smaller in the uniparental disomy group than in the deletion and control gro ups. Conclusions: The ERP results suggest that early modality specific inhibitio n is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a com mon impairment in early visual inhibition processing, uniparental disomy and par ental deletion genetic PWS subtypes clearly differ in their behavioural and brai n activation phenotypes. Significance: The present study is the first experiment al demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11- q13g in PWS result in different behaviou ral phenotype.展开更多
文摘目的探讨2例因“早发型胎儿生长受限”就诊的胎儿遗传学病因与表型之间的关联。方法收集2例胎儿的临床资料并进行羊水细胞的核型分析和染色体微阵列分析,后续抽取父母外周血确认纯合区域的来源。对其中1例病例胎盘的3处位点取样后进行荧光原位杂交分析,推测单亲二体的可能发生机制。结果2例胎儿羊水细胞的染色体核型结果均正常,微阵列分析结果提示存在16号染色体末端的纯合区域(regions of homozygosity,ROH),长度分别为6.97Mb(位于16p13.3)和16.42Mb(位于16q22.3q24.3)。经过父母和胎儿的snp位点进行分析,确定这2例胎儿为单亲同二体和单亲异二体的混合型母源16号染色体单亲二体[uniparental disomy 16,UPD(16)]。最后对其中1例胎儿胎盘3个部位取材样本的荧光原位杂交(fluorescent in situ hybridization,FISH)结果显示,胎盘绒毛细胞中16号染色体三体比例占95%以上,证实为限制性胎盘嵌合体。结论母源性16号染色体单亲二体和胎儿生长受限表型的直接关联仍需要深入研究,该表型可能是由于胎盘限制性嵌合三体所引起,我们的结果为理解16号染色体单亲二体对胎儿和胎盘的临床效应提供了新数据。
文摘Objective: Paternal deletion and maternal uniparental disomy are the principa l genetic subtypes associated with Prader- Willi syndrome (PWS). Recent clinica l findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho- physiological setup. Methods: Behaviour and event- related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT- AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT- AX task were r eaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality- specific inhibition and late gene ral inhibition, respectively. Results: The disomy group had fewer correct scores and increased reaction times as compared to the CPT- AX task than the control and deletion group. Both PWS subgroups differed significantly from the control g roup for the N200 amplitude. Only the control group showed the typical task modu lation for the N200 amplitude. The amplitude of the P300 component was considera bly smaller in the uniparental disomy group than in the deletion and control gro ups. Conclusions: The ERP results suggest that early modality specific inhibitio n is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a com mon impairment in early visual inhibition processing, uniparental disomy and par ental deletion genetic PWS subtypes clearly differ in their behavioural and brai n activation phenotypes. Significance: The present study is the first experiment al demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11- q13g in PWS result in different behaviou ral phenotype.
