Molecular Cytogenetics最新文献

Lipoblastomas (LPBs) are rare benign neoplasms derived from embryonal adipose that occur predominantly in childhood. LPBs typically present with numeric or structural rearrangements of chromosome 8, the majority of which involve the pleomorphic adenoma gene 1 (PLAG1) proto-oncogene on chromosome 8q12. Here, we report on a LPB case on which showed evidence of chromothripsis. This is the second reported case of chromothripsis in LPB.

Background: Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT.

Results: A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40-60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant.

Conclusions: Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.

Objective: To assess prenatal diagnosis and pregnancy outcomes in twin pregnancies where one fetus has nuchal translucency (NT) above the 95th percentile.

Method: In this retrospective analysis, 130 twin pregnancies (260 fetuses) in which one twin had an NT measurement above the 95th percentile while that of the other twin was normal were analyzed. Prenatal diagnostic results such as G bands, chromosomal microarray analysis, ultrasound findings, and pregnancy outcomes were reviewed.

Results: Karyotype analysis and CMA results revealed that 15 (15.6 percent, 15/96) fetuses exhibited chromosomal abnormalities and that 13 fetuses were Variant of Uncertain Significance. Chromosome abnormalities were detected at a rate of 8.9% (5/56) in the DCT group and 25.0% (10/40) in the MCT group (p = 0.033, X2 = 4.571). 2 fetuses in DCT (3.9 percent, 2/51) and 4 fetuses in MCT (13.3 percent, 4/30) (p = 0.187) revealed structural abnormalities among the cases with normal prenatal diagnosis. Fetuses in the DCT group had an overall survival rate of 75.4 percent (95/126), whereas those in the MCT group had a survival rate of 60.4 percent (81/134) (p = 0.01, X2 = 6.636). According to the findings of Logistics regression analysis, NT thickening, maternal age and method of conception were all significant risk factors for chromosome abnormalities.

Conclusion: In twin pregnancies with one fetus with NT above the 95th percentile, the prevalence of fetal structural abnormalities of the MCT group and the DCT group were comparable. Pregnant women's age and mode of pregnancy are risk factors for chromosomal abnormalities.

Objective: To investigate the efficiency of non-invasive prenatal testing (NIPT) in cases with different cutoffs of nuchal translucency (NT).

Methods: The study retrospectively analyses pregnancies with NT ≥ 2.5 mm who underwent NIPT. Results of NT, NIPT, chromosomal diagnostic and pregnancy outcomes were collected.

Results: Study group was composed of 1470 single pregnancies, including 864 with NT 2.5-2.9 mm, 350 with NT 3.0-3.4 mm and 256 with NT ≥ 3.5 mm. Non-significant differences were found in the positive predictive value (PPV) of NIPT between different cutoffs of NT. There was one false positive case with NT 4.3 mm, screening for 47,XYY in NIPT showed normal in diagnostic testing. For cases with normal NIPT results, the residual risk is 1:20 (5%, 95%CI: 0.1-10.1%) in fetuses with NT 3.0-3.4 mm and 1:15 (6.5%, 95%CI: 1.4%-11.5%) in fetuses with NT ≥ 3.5 mm. These false negative cases included one trisomy 21, seven pathogenic CNVs, one uniparental disomy and one single gene disorders.

Conclusion: Our findings demonstrated that the PPV of NIPT for screening chromosomal aberrations were similarly in different NT cutoffs, while false positive case does exist. After normal in NIPT, risk for chromosomal aberrations remained, especially pathogenic CNV and even common trisomy. Therefore, prenatal diagnosis was recommended and CMA was suggested to apply in pregnancies with NT ≥ 3.0 mm.

Purpose:  This paper presents a report on two uncommon instances of cat eye syndrome in a Chinese family.

Case presentation: The proband, a 23-year-old female, exhibited a diminutive cornea and complete blindness in her right eye, and the uncorrected distance visual acuity of her left eye was 0.7 LogMAR. Peripheral blood chromosome karyotyping reveal a karyotype of 47, XX, + mar. Subsequent analysis of chromosome copy number variation unveiled a 1.5 Mb duplication in the 22q11.1q11.21 region of the proband. The proband's mother,aged 49, displayed small eyes, wide-set eyes, downward slanting eyelids, and congenital heart disease. Chromosome copy number variation analysis also showed a 1.55 Mb duplication in the 22q11.1q11.21 region of chromosome 22 in the proband's mother. Ultimately, both members of this family were diagnosed with cat eye syndrome.

Conclusion:  Cat eye syndrome is a rare genetic disorder that greatly affects patients' lives and requires personalized treatment. This study provides new evidence for a better understanding of the diagnosis of cat eye syndrome and emphasizes the importance of genetic counseling and supervision.

Background: Down syndrome myeloid hyperplasia includes transient abnormal myelopoiesis (TAM) and the myeloid leukemia associated with Down syndrome (ML-DS). The mutation of GATA1 gene is essential in the development of Down syndrome combined with TAM or ML-DS. Some patients with TAM are asymptomatic and may also present with severe manifestations such as hepatosplenomegaly and hydrops.

Case presentation: We report two cases of prenatally diagnosed TAM. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5-8%) of trisomy 21 mosiacism by Copy Number Variation Sequencing (CNV-seq) and Fluorescence in situ hybridization (FISH). In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4(GATA1):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4(GATA1):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases.

Conclusion: It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.

Background: Balanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT).

Material and methods: From January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements.

Results: In the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6-3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1-99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages.

Conclusions: Our study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies.

Background: Many clinical studies based on spontaneous pregnancies (SPs) have demonstrated the superiority of non-invasive prenatal testing (NIPT), and the question of whether this technology is suitable for offspring conceived by assisted reproductive technology has attracted attention. This study aimed to evaluate the application value of NIPT in screening for trisomy (T)21, T18, T13 and sex chromosome aneuploidy (SCA) in pregnant women who conceived by in vitro fertilization (IVF).

Results: In total, there were 804 high-risk cases [0.88% (804/91280), singleton = 795, twin = 9] in the SP group. Among the 558 invasive prenatal diagnosis (IPD) cases (singleton = 556, twin = 2), 343 (singleton = 342, twin = 1) were true positive, including 213 cases of T21, 28 of T18, 5 of T13 and 97 (singleton = 96, twin = 1) of SCA. The positive predictive values (PPVs) of T21, T18, T13, SCA and T21/T18/T13 combined in singleton pregnancy were 89.12% (213/239), 51.85% (28/54), 21.74% (5/23), 40.00% (96/240), and 77.85% (246/316), respectively, and the PPV of SCA in twin pregnancy was 100.00%. In the IVF group, IPD was performed in 19 (singleton = 16, twin = 3) of the 27 high-risk cases [0.78% (27/3477), singleton = 16, twin = 3], of which 9 (singleton = 8, twin = 1) were true positive, including 5 cases (singleton = 4, twin = 1) of T21 and 4 of SCA. The PPVs of singleton T21, SCA and T21/T18/T13 combined were 66.67% (4/6), 50.00% (4/8) and 57.14% (4/7), respectively, and the PPV of twin T21 was 100.00% (1/1). There were no significant differences in PPV among T21, SCA and T21/T18/T13 combined in singletons between the groups (89.12% vs. 66.67%, p = 0.09; 40.00% vs. 50.00%, p = 0.57; 77.85% vs. 57.14%, p = 0.20). The sensitivity and specificity were higher for singleton and twin pregnancies in the two groups. Based on follow-up results, 1 case of false negative T21 was found in the singleton SP group. Additionally, the mean foetal fraction (FF) of the IVF group was lower than that of the SP group (11.23% vs. 10.51%, p < 0.05).

Conclusion: NIPT has high sensitivity and specificity in screening chromosomal aneuploidies in both IVF pregnancy and spontaneous pregnancy, so it is an ideal screening method for IVF pregnancy.

Background: Cytogenetic analysis continues to have an important role in the management of acute myeloid leukemia (AML) because it is essential for prognostication. It is also necessary to diagnose specific categories of AML and to determine the most effective form of treatment. Reports from South Asia are few because the availability of cytogenetic services is relatively limited.

Methods: We performed a retrospective analysis of the cytogenetic findings in adults with AML seen consecutively in a single centre in India. The results were categorised according to the 2022 World Health Organisation (WHO), International Consensus Classification (ICC) and European LeukemiaNet (ELN) classifications.

Results: There were 1791 patients aged 18-85 years (median age 42, 1086 males). Normal karyotypes were seen in 646 (36%) patients. The 1145 (64%) abnormal karyotypes comprised 585 (32.7%) with recurrent genetic abnormalities (RGA), 403 (22.5%) with myelodysplasia-related cytogenetic abnormalities (MRC), and 157 (8.8%) with other abnormalities. There were 567 (31.7%) patients with solitary abnormalities and 299 (16.7%) with two abnormalities. Among the 279 (15.6%) patients with ≥ 3 abnormalities, 200 (11.2%) had complex karyotypes (CK) as per the WHO/ICC and 184 (10.3%), as per the ELN definition. There were 158 (8.8%) monosomal karyotypes (MK). Patients with normal karyotypes had a higher median age (45 years) than those with abnormal karyotypes (40 years, p < 0.001), and those with ≥ 3 abnormalities (43 years), than those with fewer abnormalities (39 years, p = 0.005). Patients with CK (WHO/ICC) and monosomal karyotypes had a median age of 48 years. Those with RGA had a lower median age (35 years, p < 0.001) than MRC (46 years) or other abnormalities (44 years). The t(15;17) was the most common abnormality (16.7%),followed by trisomy 8 (11.6%), monosomy 7/del 7q (9.3%), t(8;21) (7.2%), monosomy 5/del 5q (6.7%) and monosomy 17/del 17p (5.2%).

Conclusion: Our findings confirm the lower age profile of AML in India and show similarities and differences with respect to the frequencies of individual abnormalities compared to the literature. The frequencies of the t(15;17), trisomy 8 and the high-risk abnormalities monosomy 7 and monosomy 5/del 5q were higher, and that of the inv(16), lower than in most reports.

Background: Small supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome of unknown origin by conventional cytogenetics. The understanding of clinical significance of sSMC is still limited in prenatal diagnosis. The presence of sSMC poses a challenge for genetic counselling.

Methods: We obtained the clinical information of 25 cases with sSMC. The fetal samples were subjected to multiple molecular and cytogenetic approaches including karyotype analysis, chromosomal microarray analysis, bacterial artificial chromosomes-on-beads assay, and fluorescence in situ hybridization.

Results: Seven sSMCs were found to be r(X), and five of the cases terminated the pregnancy. Three markers were idic(15), and one of the cases was normal at birth. Two markers were i(12p), and both cases terminated the pregnancy. Other markers were r(Y) (outcome: normal at birth), i(18p) (outcome: stillbirth), der(15) (outcome: terminated), del(9) (outcome: terminated), dup(13) (outcome: follow-up loss), and derived from chromosome 21 (outcome: stillbirth). Seven markers were of unknown origin because not all methods were applied to them.

Conclusion: Applying multiple molecular and cytogenetic approaches could identify the origin and genetic content of sSMC to assist the genetic counselling in prenatal diagnosis.