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We report a prenatally diagnosed case of partial trisomy 2p and partial monosomy 3p, resulting from unbalanced translocation (2;3)(p25.1;p25.3) of paternal origin. Parents were non consanguineous Caucasians, with familial history of recurrent miscarriages on the father's side. Detailed sonographic examination of the fetus showed a septated cystic hygroma measuring 6 mm at 13 weeks' gestation. Karyotyping and fluorescent in situ hybridization (FISH) analysis of cultured amniotic fluid cells revealed an unbalanced translocation der(3)t(2;3)(p25.1; p25.3) and apparently balanced inv(3)(p13p25.3) in a fetus. Parental cytogenetic evaluation using karyotyping and FISH analysis showed the presence of both a balanced translocation and a paracentric inversion in father t(2;3) (p25.1;p25.3) inv(3)(p13p25.3). Microarray analysis showed a 11.6 Mb deletion at 3p26.3-p25.3 and duplication of 10.5 Mb at the 2p25.3-p25 region. The duplicated region at 2p25.1p25.3 contains 45 different genes, where 12 are reported as OMIM morbid genes with different phenotypical implications. The deleted region at 3p26.3-p25.3 contains 65 genes, out of which 27 are OMIM genes. Three of these (CNTN4, SETD5 and VHL) were curated by Clingene Dosage Gene Map and were given a high haplo-insufficiency score. Genes affected by the unbalanced translocation could have contributed to some specific phenotypic changes of the fetus in late pregnancy. The application of different cytogenetic methods was essential in our case, allowing the detection of different types of structural chromosomal aberrations and more thorough genetic counseling for future pregnancies. [ABSTRACT FROM AUTHOR]

Background: The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for not only intrachromosomal deletions and duplications but also small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome. Further characterization of copy number changes and methylation patterns in these sSMC(15)s could lead to better understanding of their phenotypic consequences. Methods: Routine G-band karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay were performed on two Chinese patients with a sSMC(15). Results: Patient 1 showed an isodicentric 15, idic(15)(q13), containing symmetrically two copies of a 7.7 Mb segment of the 15q11-q13 region by a BP3::BP3 fusion. Patient 2 showed a ring chromosome 15, r(15)(q13), with alternative one-copy and two-copy segments spanning a 12.3 Mb region. The defined methylation pattern indicated that the idic(15)(q13) and the r(15)(q13) were maternally derived. Conclusions: Results from these two cases and other reported cases from literature indicated that combined karyotyping, aCGH and MS-MLPA analyses are effective to define the copy number changes and methylation patterns for sSMC(15)s in a clinical setting. The characterized genomic structure and epigenetic pattern of sSMC(15)s could lead to further gene expression profiling for better phenotype correlation. [ABSTRACT FROM AUTHOR]

Abstract: We report a 20-month-old girl ascertained at the age of 11months for developmental delay. She presented with hypotonia and delayed motor development. The patient had severe language impairment and showed behaviour consistent with autism spectrum disorder. She was microcephalic with mild dysmorphic features and had joint hyperlaxity. We detected a 2.3Mb de novo deletion in 2q24.2q24.3 on her paternal chromosome. We compare the clinical features of our patient to six previously published patients with a deletion in 2q24.2q24.3, and one patient reported in the ECARUCA database. Although the clinical presentation of these patients is not highly consistent, likely due to the different deletion size and gene content, the following features seem to be recurrent: disturbance in the central nervous system, poor growth, hypotonia, and joint hyperlaxity. The region deleted in our patient contains 13 genes including PSMD14, TBR1, SLC4A10, DPP4, KCNH7, and FIGN. We briefly review the knowledge of these genes and their possible involvement in the aetiology of this developmental delay syndrome. [Copyright &y& Elsevier]

Abstract: Supernumerary marker chromosomes (SMC) are heterogeneous group of chromosomes which are reported in variable phenotypes. Approximately 70% originate from acrocentric chromosomes. Here we report a couple with recurrent miscarriages and a SMC originating from an acrocentric chromosome. The cytogenetic analysis of the husband revealed a karyotype of 47,XY+marker whereas the wife had a normal karyotype. Analysis of SMC with C-banding showed the presence of a big centromere in the center and silver staining showed prominent satellites on both sides of the marker. Apparently, microarray analysis revealed a 2.1Mb duplication of 15q11.2 region but molecular cytogenetic analysis by fluorescence in situ hybridization (FISH) with whole chromosome paint (WCP) 15 showed that the SMC is not of chromosome 15 origin. Subsequently, FISH with centromere 22 identified the SMC to originate from chromosome 22 which was also confirmed by WCP 22. Additional dual FISH with centromere 22 and Acro-p-arm probes confirmed the centromere 22 and satellites on the SMC. Further fine mapping of the marker with Bacterial Artificial Chromosome (BAC) clones; two on chromosome 22 and four on chromosome 15 determined the marker to possess only centromere 22 sequences and that the duplication 15 exists directly on chromosome 15. In our study, we had identified and characterized a SMC showing inversion duplication 22(p11.1) combined with a direct tandem duplication of 15q11.2. The possible genotype–phenotype in relation with the two rearrangements is discussed. [Copyright &y& Elsevier]

Abstract: We report a molecular cytogenetic characterization of 17p13.3 deletion syndrome by array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) in a fetus with lissencephaly, corpus callosum dysgenesis, ventriculomegaly, microcephaly, intrauterine growth restriction (IUGR), polyhydramnios and single umbilical artery. aCGH analysis revealed a 3.17-Mb deletion at 17p13.3, or arr [hg19] 17p13.3 (0–3,165,530)×1. The qPCR assays revealed a maternal origin of the deletion. Metaphase FISH analysis detected the absence of the LIS1 probe signal on the aberrant chromosome 17. The karyotype was 46,XX,del(17)(p13.3). We review the literature of chromosome 17p13.3 deletion syndrome with prenatal findings and diagnosis, and suggest that prenatal ultrasound detection of central nervous system anomalies such as lissencephaly, corpus callosum dysgenesis/agenesis, ventriculomegaly and microcephaly associated with IUGR, polyhydramnios, congenital heart defects, abdominal wall defects and renal abnormalities should include a differential diagnosis of chromosome 17p13.3 deletion syndrome. [Copyright &y& Elsevier]

Abstract: We present prenatal diagnosis of de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14) and molecular cytogenetic characterization of the deletion using uncultured amniocytes. We review the phenotypic abnormalities of previously reported patients with similar proximal interstitial 4p deletions, and we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that are deleted within this region. [Copyright &y& Elsevier]

Abstract: We present an 8-year-old girl with cleidocranial dysplasia, psychomotor developmental delay, poor wound healing and a 6p21.2–p12.3 deletion detected by aCGH. The patient was previously found to have a normal karyotype on conventional cytogenetic analysis and no RUNX2 mutation on sequence analysis. We discuss the genotype–phenotype correlation and the consequence of haploinsufficiency of CUL7, VEGFA, NFKBIE and RUNX2 in this case. [Copyright &y& Elsevier]

There is strong evidence that multistep tumorigenesis begins with the acquisition of somatic mutations which promote genomic instability. Genomic instability is an important malignant trait because genomic instability can generate the genetic diversity that is necessary for the transforming cell to acquire increasingly variable and aggressive tumor phenotypes. Genomic instability often manifests in the form of chromosomal instability (CIN) leading to the induction of aneuploidy, a phenomenon identified by high resolution molecular cytogenetic techniques. Fluorescent in situ hybridization (FISH) and Array Comparative Genomic Hybridization (aCGH) are two high resolution molecular cytogenetic techniques that allow detection of chromosomal aneuploidy and structural rearrangements occurring in pre-malignant and malignant lesions during tumor progression and invasion. These high resolution molecular cytogenetic techniques are used for genetic screening of single cells in pre-malignant and precursor malignant lesions as well as in exfoliated cells from body fluids and excreta. Consequently, molecular cytogenetic testing offers the promise of an extremely powerful method of risk assessment and early detection of cancer. [ABSTRACT FROM AUTHOR]

Abstract: From the investigation by microarray-based comparative genomic hybridization (aCGH), a new syndrome with “atypical” proximal interstitial deletion of 1p36.23-36.11 has been suggested. Here, we report on an 8.5-year-old girl with psychomotor developmental delay and a dysmorphic appearance. Although her G-banded chromosomal analysis showed inv(3)(p14.1q26.2), detailed FISH analyses denied pathogenic deletions around the breakpoints of chromosome 3. Accordingly, aCGH analysis was performed to identify a genomic aberration related to her phenotype, and a 3.5-Mb interstitial deletion of 1p36.13-36.12 was revealed. This deletion was the most proximal interstitial deletion of 1p36. Compared to the previously reported patients, abnormally shaped teeth, delayed tooth eruption, and leg malformation are unique phenotypes only to this patient, which might be due to the centromeric unique deletion region with 0.8-Mb. [Copyright &y& Elsevier]

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements, and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested an under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized. [ABSTRACT FROM AUTHOR]