Prenatal diagnosis of Pallister-Killian syndrome and literature review

Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.     

非标记表面增强拉曼光谱在DNA检测中的应用

表面增强拉曼光谱(SERS)是一种超灵敏的生化分析技术,已经被广泛运用于细胞、核酸、蛋白质等生物分子的检测,在生物医学领域表现出了巨大的应用潜力。近年来,将表面增强拉曼光谱技术应用于遗传物质DNA的精准检测,引起了人们广泛的关注。本文简要叙述了表面增强拉曼光谱技术的基本原理及其在DNA检测中的优势,主要介绍了非标记的DNA-SERS检测应用进展,其中包括本项目组的相关工作。研究表明,非标记DNA-SERS技术有望成为一种快速、准确的临床诊断方式。     

基于光谱技术的产前检测方法研究进展

优生优育是我们重要的国策。自二胎政策颁布以来,高龄产妇数量呈现明显上升的趋势,先天性畸形儿的发生几率变大。传统的产前检测方法存在较高流产风险、灵敏度低、耗时等问题,探寻一种无损快捷、经济灵敏的产前检测方法至关重要。本文首先介绍了常见的胎儿出生缺陷及当前临床常见的产前检测方法的优缺点,重点综述了光谱技术的特点及其在产前检测中的应用。其中包括光谱核型、实时荧光定量PCR、SNP等位基因位点分析等利用荧光光谱分析方法和拉曼光谱在产前检测中的应用情况。特别阐述了表面增强拉曼光谱SERS在生物检测中的优势,最后总结并展望了SERS光谱在产前检测的应用。     

Positive predictive value of noninvasive prenatal testing for sex chromosome abnormalities

Molecular Biology Reports - Early and intermediate serological screening cannot detect sex chromosome abnormalities. Currently, noninvasive prenatal testing (NIPT) is the only procedure available...     

黑果腺肋花楸扦插生根特性及不定根发生模式研究

【目的】为了解黑果腺肋花楸扦插不定根起源及发育过程,揭示其扦插生根机理。【方法】以‘福康源1号’当年生半木质化插穗为研究材料,利用水培扦插技术和石蜡切片法对不定根形成过程中插穗内部组织结构及外部形态的变化规律进行观察。【结果】在水培条件下,IBA处理扦插生根期为30~40 d,扦插过程中皮孔处10~15 d出现不定根,插穗切口处15~20 d出现不定根,生根速度、不定根数量及根长均优于对照,外源诱导可显著提高生根率和生根质量。扦插前的插穗内无潜伏根原基存在,不定根原基在插后形成;不定根形成为愈伤组织生根型和内部分生组织生根型。皮部产生的不定根起源于维管形成层、韧皮薄壁细胞或皮层;愈伤组织产生的不定根是由愈伤组织内的薄壁细胞团特化而成;叶隙或枝隙是形成不定根原基和产生愈伤组织的主要区域。【结论】扦插生根属于多位点发生模式,属于诱导生根型。     

High expression levels of pyrimidine metabolic rate–limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets

Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

     

Chromosomal microarray analysis for pregnancies with abnormal maternal serum screening who undergo invasive prenatal testing

Recently, chromosomal microarray analysis (CMA) has been implemented as a first-tier test in pregnancies with ultrasound anomalies. However, its application for pregnancies with abnormal maternal serum screening (AMSS) only is not widespread. This study evaluated the value of CMA compared to traditional karyotyping in pregnancies with increased risk following first- or second-trimester maternal serum screening. Data from 3973 pregnancies with referral for invasive prenatal testing following AMSS were obtained from April 2016 to May 2020. Routine karyotyping was performed and single nucleotide polymorphism array was recommended. The foetuses were categorized according to the indications as AMSS only (group A) and AMSS with ultrasound anomalies (group B). CMA was performed on 713 prenatal samples. The proportion of women opting for CMA testing in both groups increased over the years. The incremental yield of clinically significant findings for pregnancies with high risk of screening results was similar to that for the foetuses with ultrasound soft markers (P > 0.05), but significantly lower than that for the foetuses with structural anomalies (P < 0.05). The total frequencies of variants of unknown significance in groups A and B showed no significant difference (P > 0.05). CMA should be performed for pregnant women undergoing prenatal invasive testing due to AMSS, especially with high-risk results, regardless of ultrasound findings.     

Prenatal diagnosis of 22q11.2 copy number abnormalities in fetuses via single nucleotide polymorphism array

Molecular Biology Reports - The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different...     

Pathogenic copy number variations are associated with foetal short femur length in a tertiary referral centre study

Shortened foetal femur length (FL) is a common abnormal phenotype that often causes anxiety in pregnant women, and standard clinical treatments remain unavailable. We investigated the clinical characteristics, genetic aetiology and obstetric pregnancy outcomes of foetuses with short FL and provided a reference for perinatal management of such cases. Chromosomal microarray analysis was used to analyse the copy number variations (CNV) in short FL foetuses. Of the 218 foetuses with short FL, 33 foetuses exhibited abnormal CNVs, including 19 with pathogenic CNVs and 14 with variations of uncertain clinical significance. Of the 19 foetuses with pathogenic CNVs, four had aneuploidy, 14 had deletions/duplications, and one had pathogenic uniparental diploidy. The 7q11.23 microdeletion was detected in three foetuses. The severity of short FL was not associated with the rate of pathogenic CNVs. The duration of short FL for the intrauterine ultrasound phenotype in foetuses carrying a pathogenic CNV was independent of the gestational age. Further, maternal age was not associated with the incidence of foetal pathogenic CNVs. Adverse pregnancy outcomes occurred in 77 cases, including termination of pregnancy in 63 cases, postnatal dwarfed foetuses with intellectual disability in 11 cases, and three deaths within 3 months of birth. Pathogenic CNVs closely related to foetal short FL were identified, among which the 7q11.23 microdeletion was highly associated with short FL development. This study provides a reference for the perinatal management of foetuses with short FL.