Low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome

ObjectiveWe present low-level mosaic trisomy 13 at amniocentesis in a pregnancy associated with a positive non-invasive prenatal testing (NIPT) result suspicious of trisomy 13, a chorionic villus sampling (CVS) result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.Case reportA 29-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a positive NIPT result (Z-score = 20.9, positive ≥3) suspicious of trisomy 13 at 11 weeks of gestation and a CVS result of mosaic trisomy 13 at 14 weeks of gestation. At 14 weeks of gestation, CVS revealed the multiplex ligation-dependent probe amplification (MLPA) result of rea X,Y (P095) × 1, 13 (P095) × 3, 18,21 (P095) × 2/X,Y (P095) × 1, 13,18,21 (P095) × 2 and a karyotype of 48,XY,+13,+mar [9]/47,XY,+mar[16]. She was referred to the hospital for genetic counseling at 15 weeks of gestation, and cytogenetic analysis of parental blood revealed 47,XY,+mar in the father and 46, XX in the mother. Fluorescence in situ hybridization (FISH) analysis on the paternal blood showed that the extra dicentric marker was derived from chromosome 15 without the locus SNRPN (15q11.2), and the result was 47,XY,+mar.ish dic(15) (D15Z1++, SNRPN-, PML-)[20]. Amniocentesis at 20 weeks of gestation revealed a karyotype of 47,XY,+mar pat (20/20). Simultaneous interphase FISH analysis on uncultured amniocytes revealed 32% (32/100 cells) mosaicism for trisomy 13. Quantitative fluorescence polymerase chain reaction (QF-PCR) analysis using the DNA extracted from the parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 13. Prenatal ultrasound findings were normal. The woman was advised to continue the pregnancy, and a phenotypically normal 2708-g male baby was delivered at 38 weeks of gestation, The cord blood, umbilical cord and placenta had the karyotypes of 47,XY,+mar pat and did not have UPD 13. When follow-up at age two months, the neonate was phenotypically normal. FISH analysis on buccal mucosal cells detected 5.3% (5/95 cells) mosaicism for trisomy 13, compared with 0% in the normal control.ConclusionLow-level mosaic trisomy 13 at amniocentesis can be associated with a positive NIPT result suspicious of trisomy 13, a CVS result of mosaic trisomy 13, cytogenetic discrepancy in various tissues and a favorable fetal outcome.     

Low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with a negative NIPT result,cytogenetic discrepancy in various tissues,perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome

ObjectiveWe present low-level mosaic trisomy 21 at amniocentesis associated with a favorable fetal outcome.Case reportA 31-year-old primigravid woman underwent non-invasive prenatal testing (NIPT) at 12 weeks of gestation, and the result was normal. She underwent amniocentesis at 16 weeks of gestation because of fetal choroid plexus cyst, and the result was 47,XX,+21[5]/46,XX[32]. Repeat amniocentesis was performed at 19 weeks of gestation, and the result was 47,XX,+21[5]/46,XX[15]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr (21) × 3 [0.10], consistent with 10% mosaicism for trisomy 21. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 22 weeks of gestation, and the third amniocentesis was performed at 25 weeks of gestation, and the result was 46,XX (20/20 colonies). The parental karyotypes were normal. Simultaneous quantitative fluorescence polymerase chain reaction (QF-PCR) analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy (UPD) 21. aCGH analysis on uncultured amniocytes revealed arr 21q11.2q22.3 × 2.1 (log₂ ratio = 0.1), consistent with 10–15% mosaicism for trisomy 21. Fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 30% (30/100 cells) mosaicism for trisomy 21. The woman was advised to continue the pregnancy, and a phenotypically normal 2800-g female baby was delivered at 38 weeks of gestation. The karyotype of cord blood, umbilical cord and placenta were 47,XX,+21[1]/46,XX[39]. 47,XX,+21[4]/46,XX[36] and 46,XX (40/40 cells), respectively. When follow-up at age two months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XX,+21[1]/46,XX[39], and FISH analysis on buccal mucosal cells revealed 8.4% (7/83 cells) mosaicism for trisomy 21, compared with 0% in the normal control.ConclusionLow-level mosaic trisomy 21 at amniocentesis can be associated with a negative NIPT result, cytogenetic discrepancy in various tissues, perinatal progressive decrease of the aneuploid cell line and a favorable fetal outcome.     

北京地区78例性染色体异常患者的细胞遗传学分析

目的探讨78例性染色体异常患者的临床表现并进行细胞遗传学分析。方法对患者外周血淋巴细胞行染色体常规G显带核型分析。结果 78例性染色体异常核型中,性染色体数目异常51例,占异常核型的65.38%;性染色体结构异常12例,占15.39%;Y染色体形态异常11例,占14.10%;另外还有性反转综合征4例,占5.13%。结论性染色体异常可导致性分化异常或生殖异常、智力低下等遗传效应,对患者进行染色体的检查,将有助于临床诊断和治疗。     

司帕沙星对哺乳动物培养细胞染色体畸变试验

司帕沙星对中国仓鼠肺成纤维细胞(CHL)LC_(50)为136μg/ml。司帕沙星浓度为35.70和140μg/ml时不加或加S_9mix均未发现CHL细胞明显的染色体损伤,畸变率为5％以下,试验结果判为阴性。     

Adult sclerosing rhabdomyosarcoma: cytogenetic link with embryonal rhabdomyosarcoma

Rhabdomyosarcomas are classified into three well-defined categories: embryonal, alveolar and pleomorphic rhabdomyosarcoma. Recently, seven cases of an unusual adult type of rhabdomyosarcoma with a prominent hyaline sclerosis have been described. We report the hitherto unreported cytogenetic changes of an adult sclerosing rhabdomyosarcoma. A 79-year-old woman underwent an amputation for a rapidly growing soft tissue mass in the anterior compartment of the right lower leg. The tumor infiltrated the tibia. On histology, a fascicular spindle to round cell proliferation, embedded in a prominent hyaline matrix, was seen. Immunohistochemistry showed focal desmin, myogenin and MyOD1 expression, and electron microscopy revealed Z-band material. Cytogenetic analysis disclosed a 44–49,XX,+del(1)(p22)[2],+11,+16[5],+18[12],+21[3],-22 [cp13] karyotype. Using fluorescent in situ hybridization (FISH) analysis, the tumor cells were negative for FOXO1A-disrupting translocations specific for alveolar rhabdomyosarcoma. The chromosomal composition of malignant cells resembled the pattern of numerical changes frequently observed in embryonal rhabdomyosarcoma, suggesting a close relationship of an adult sclerosing rhabdomyosarcoma with this entity.     

Prenatal diagnostic testing among women referred for advanced maternal age in Beijing, 2001–2012

Objective

To determine the proportion of women with advanced maternal age (AMA) undergoing amniocentesis and assess the recommended indication of 35 years or older in China.

Methods

Data were retrospectively evaluated from 9641 patients who underwent diagnostic prenatal amniocentesis in Beijing, China, between January 2001 and December 2012. Maternal age, indication for testing, and karyotype data were collected. Patients referred for AMA were stratified in 2 ways: 35–37 years, 38–40 years, and 41 years or older; and indication of AMA alone or combined with other screening. Outcomes and safety performance were compared among the groups.

Results

From 2001 to 2012, the annual rate of amniocentesis and the proportion of AMA-related indications increased (P < 0.01). Overall, 82 abnormalities were detected. In the AMA group, the spontaneous abortion rate was 0.5% (22/4748). The positive predictive value (PPV) of AMA alone was 0.5% for women aged 35–37 years. Only among women aged 41 years or older was the PPV of AMA alone better than that of AMA plus other indications (2.3% vs 1.5%, respectively).

Conclusion

The PPV of 35 years or older did not offset the risk of spontaneous abortion. AMA alone should not be used as an indication for amniocentesis especially among women aged 35–40 years.     

新药对分子遗传学异常的多发性骨髓瘤患者预后的影响

多发性骨髓瘤(MM)是一种异质性疾病,常伴随多种分子遗传学异常,如1q21扩增,t(4;14)、17p缺失等.这些分子遗传学异常的出现常提示预后不良.随着沙利度胺、来那度胺及硼替佐米等新药的广泛使用,MM的生存得到显著提高.目前许多研究显示部分新药能克服或至少部分克服某些分子遗传学异常对预后的不良影响,但这些新药对分子遗传学异常的影响仍存在较大的争议.文章通过对近些年来新药对分子遗传学异常MM患者的预后影响作一综述,以期为临床治疗提供帮助.     

Sister chromatid exchange, (SCE), High-Frequency Cells (HFCs) and SCE distribution patterns in peripheral blood lymphocytes of Spanish adult smokers compared to non-smokers

According to the International Agency for Research on Cancer, smoking tobacco is a major cause of cancer in humans. It causes about half of all male cancer deaths and an ever increasing number of cancer deaths in females. The aim of this study was to establish whether cigarette smoking increases sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in two Spanish population groups; light and heavy smokers. The mean number of High-Frequency Cells (HFCs) was determined and, the SCE distribution pattern among the chromosomes was analysed represented by a ratio described below. A local sample of 101 adult smokers (n = 48) and non-smokers (n = 53), aged from 18 to 49 years, was studied using SCE levels in peripheral lymphocytes. Heavy smoking (⩾10 cigarettes per day) increased significantly the SCE frequency and the HFC parameters. Neither age nor sex significantly influenced the frequencies in the groups studied.     

Radiation-induced meningiomas: clinical, cytogenetic, and microarray features

Limited information exists about the clinical and biological features of radiation-induced meningiomas (RIMs), particularly those that follow high-dose therapeutic radiation. We report our experience with 20 patients with RIMs (16 following high-dose radiotherapy) treated at our institution from 1993-2006. Patients (14 female, 6 male) had intervals from first radiotherapy to RIM diagnosis of 11-63 years; 12 had at least one RIM occur at an interval of 30 years or more after initial radiotherapy. Multiple RIMs were seen in six patients, with one patient developing his six RIMs sequentially over a 22-year interval. Most RIMs could be managed surgically, either with a single extensive resection or additional resection(s). Adjuvant stereotactic radiosurgery, external beam radiation, or chemotherapy were required in a minority (n = 6). Most were WHO grade I meningiomas. Complex karyotypes were found in three of four cases and abnormalities of chromosome 1p and/or LOH 1p36 were identified in five of 11 informative cases. Gene-expression microarray analysis of RIMs (n = 5) compared to non-RIMs (MEN, n = 6) and a panel of other tumors (n = 62) showed that RIM gene-expression was similar to that seen in MEN, and by clustering analysis did not separate from them. However, microarray comparative gene-expression analysis did demonstrate a few genes with significant differences in the expression level in RIM versus MEN. Of note, NF2 was under-expressed in four of five RIMs (P = 0.0065), at a similar level as measured in MEN.