A HhaI/BstUI polymorphism in a novel gene at human chromosome 11p15.5

We found a HhaI/BstUI polymorphism in the 3′ untranslated region of a novel gene which was localized to 11p15.5. This region is one of prominent imprinting domains and contains multiple imprinted genes, such as H19, IGF2 , KVLQT1, and p57 ^KIP2 , which suggests that regional factors might contribute to the imprinting. This polymorphism will be useful in the allelic analysis of expression and methylation of the novel gene. Received: July 24, 1998 / Accepted: July 29, 1998     

Amnesic effects of bilateral lesions placed in the hyperstriatum ventrale of the chick after imprinting

Summary The purpose of this study was to investigate whether bilateral lesions to a part of the hyperstriatum ventrale (IMHV) impair retention if they are placed after chicks have been imprinted. Domestic chicks were hatched and reared in darkness and exposed to an imprinting (training) stimulus for 2 h commencing 22 h post hatch. The chicks were then anaesthetised and bilateral lesions placed in IMHV (N = 16) birds, hyperstriatum accessorium (HA; N = 16) or the lateral part of the cerebral hemispheres (LCA; N = 16). Forty-eight sham-operated chicks served as controls. Chicks were returned to the dark incubator, and, 15–20 h after the operation, their approach towards the training stimulus and to a second novel stimulus was measured. The controls and the chicks with lesions in HA and LCA showed a strong preference for the training stimulus and hence a high level of retention. The preferences of these three experimental groups did not differ significantly from one another. The mean preference of chicks with lesions in IMHV was significantly less than that of the sham-operated controls (P<0.01) and of chicks lesioned in HA (P<0.05). Bilateral lesions to IMHV therefore selectively impair retention of a preference acquired through imprinting. This impairment is unlikely to be a non-specific consequence of defective sensory processing or motor performance because the four groups did not differ from each other in (i) the time taken accurately to peck a rocking bead, (ii) the accuracy of pecking millet seeds and (iii) the performance of a simultaneous visual discrimination task involving heat reinforcement.Supported by grants from the Science Research Council, the Leverhulme Trust, the Wellcome Trust and FAPESP (Brazil)     

Contribution of GRB10 to the prenatal phenotype in Silver-Russell syndrome? Lessons from 7p12 copy number variations

The growth factor binding protein 10 (GRB10) has been suggested as a candidate gene for Silver-Russell syndrome because of its localization in 7p12, its imprinting status, data from mice models and its putative role in growth. Based on a new patient with normal growth carrying a GRB10 deletion affecting the paternal allele and data from the literature, we conclude that the heterogeneous clinical findings in patients with copy number variations (CNVs) of GRB10 gene depend on the size and the gene content of the CNV. However, evidence from mouse and human cases indicate a growth suppressing role of GRB10 in prenatal development. As a result, an increase of active maternal GRB10 copies, e.g. by maternal uniparental disomy of chromosome 7 or duplications of the region results in intrauterine growth retardation. In contrast, a defective GRB10 copy might result in prenatal overgrowth, whereas the paternal GRB10 allele is not required for proper prenatal growth.     

STRUCTURED THERAPY INTERRUPTION (STI) AND DECEPTIVE IMPRINTING

The immune response in individuals chronically infected with HIV-1 is unable to prevent progression of disease. Diversion of immune recognition via ‘Deceptive Imprinting’ allows virus variants to continue the infection. Stuctured Interrupting of (HAART) therapy (STI) causes rebound of virus with ‘wild-type’ strains that stimulate the immune system. Combining STI with suppression of the dominant response against anti-wild–type virus is proposed to enhance the beneficial effects of STI.     

Silver-Russell syndrome in a girl born after <Emphasis Type="Italic">in vitro</Emphasis> fertilization: partial hypermethylation at the differentially methylated region of <Emphasis Type="Italic">PEG1</Emphasis>/<Emphasis Type="Italic">MEST</Emphasis>

Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART. Partial hypermethylation was identified at the differentially methylated region of paternally expressed PEG1/MEST in a girl with Silver-Russell syndrome born after in vitro fertilization.     

STOX1 gene in pre-eclampsia and intrauterine growth restriction

The STOX1 gene, identified as a candidate gene for pre-eclampsia in Dutch women, is placentally expressed and subject to imprinting with preferential transmission of the maternal allele. In our study, STOX1 -Y153H frequencies were similar in 157 women with pre-eclampsia (65%) and in 157 controls (64%) from the general Dutch population. In an isolated Dutch population, a distortion could not be demonstrated in the transmission of STOX1 -Y153H variation from heterozygous mothers to offspring in 50 and 56 families with pregnancies complicated by pre-eclampsia or intrauterine growth restriction, respectively. Our findings do not confirm previous suggestions that STOX1 plays a major role in Dutch women with pre-eclampsia.     

前列腺癌组织中IGF-Ⅱ的基因印迹状态及其临床意义

背景与目的：我国前列腺癌的发病率逐年上升,就诊时多为晚期患者,内分泌治疗后有效期短,继续治疗困难。胰岛素样生长因子Ⅱ（insulin—like growth factorⅡ,IGF-Ⅱ）可促进多种细胞的增殖,抑制细胞凋亡：其表达受到基因印迹的调控．且基因印迹状态的改变与多种肿瘤的发生相关。本研究拟检测晚期前列腺癌组织中IGF-Ⅱ的印迹状态,并探讨印迹基因丢失与疾病进展的关系。方法：应用限制性酶切片段长度多态性分析法（restrictive fragmentle．gthpo lymorphism,RFLP）．检测41例前列腺癌、27例前列腺增生和13例正常前列腺组织中的IGF-Ⅱ基因印迹状态。结果：前列腺癌、前列腺增生和正常前列腺组织中IGF—Ⅱ杂合子基因型分别为70．7％（29／41）、55．5％（15／27）和61．5％（8／13）;58．6％（17／29）的前列腺癌组织中发生了IGF-Ⅱ的印迹丢失,高于前列腺增生组织（13.3％,P〈0．05）和正常前列腺组织（12．5％,P〈0．05）中的印迹丢失率。IGF-Ⅱ基因印迹状态与前列腺癌患者年龄无相关性．也与内分泌治疗前患者的血前列腺特异抗原值、伴发骨转移以及癌细胞的分化程度无显著相关。而全雄激素阻断治疗后,有印迹丢失的前列腺癌患者的1年无疾病进展生存率较无印迹丢失的患者低（70．0％vs．100．0％,P=0．039）。结论：晚期前列腺癌组织中IGF-Ⅱ基因印迹丢失发生率明显增高．并且印迹丢失与前列腺癌内分泌治疗后的进展恶化相关。     

SGCE基因变异致儿童肌阵挛肌张力障碍综合征临床特点及基因分析

目的探讨SGCE基因变异导致儿童期起病的肌阵挛肌张力障碍综合征患儿的临床特点及基因分型.方法收集2018年5月至2019年10月首都医科大学附属北京儿童医院神经内科和北京大学第一医院儿科共同收集的9例经全外显子组测序方法以及多重链接依赖的探针扩增技术确诊的SGCE基因变异导致的肌阵挛肌张力障碍综合征患儿的临床资料,并对患儿进行随访,对临床特点及基因变异结果进行回顾性总结分析.结果9例患儿中男4例、女5例,起病年龄1岁~3岁2月龄.首发症状为肌阵挛者4例,肌张力障碍者5例.病程中,9例均有肌阵挛症状,8例有肌张力障碍症状.8例肌阵挛表现为双上肢不自主抖动.6例病程中曾有下肢突然抖动一下,导致步态不稳甚至跌倒.肌张力障碍症状表现为行走姿势异常,其中5例右下肢受累,3例左下肢受累.3例有阳性家族史.9例患儿智力发育均正常.发作期及发作间期视频脑电图未见明显异常,肌电图及头颅磁共振成像正常.基因结果示9例携带SGCE基因变异,其中3例为移码变异,2例为无义变异,2例为错义变异,1例为大片段缺失变异,1例为剪切位点变异;7例为遗传性变异,均为父源,2例为新生变异.治疗上,8例加用美多芭口服,6例肌阵挛较前有所减少,走路姿势不同程度改善.4例加用硝西泮,2例有效.结论SGCE基因变异可导致肌阵挛肌张力障碍综合征,多在幼儿期或学龄前期起病,肌阵挛和肌张力障碍均可为首发症状.非癫痫性肌阵挛是其突出症状,且有上肢优势特点.绝大多数病程中伴肌张力障碍,部分肌张力障碍可自行缓解.SGCE基因为母源印记基因,遗传性变异多为父源.