Prenatal Diagnosis and Molecular Cytogenetic Characterization of a Small Supernumerary Marker Chromosome Derived from Chromosome 18 and Associated With a Reciprocal Translocation Involving Chromosomes 17 And 18

SummaryObjectivePrenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to identify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation.Materials, Methods and ResultsA 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chromosome 18 centromeric signal (cep18). The derivative chromosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2), +mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18.ConclusionOur case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences

Prenatal detection and characterization of a psu idic(8)(p23.3) which likely derived from nonallelic homologous recombination between two MYOM2-repeats

Mosaicism with an isodicentric 8 with a breakpoint at p23.3 [idic(8)(p23.3)] is very rare. We report the first prenatal case on a male fetus, in which obstetric ultrasound revealed multiple congenital anomalies at 28 weeks of gestation. Cytogenetic analysis of amniocytes showed mos 45,XY,-8,psu idic(8)(p23.3)[16]/46,XY,psu idic(8)(p23.3)[4], and that of cord blood lymphocytes revealed mos 46,XY, psu idic(8)(p23.3)[37]/45,XY,-8,psu idic(8)(p23.3)[13]. Fluorescence in situ hybridization studies revealed that the break-reunion occurred at the cytoband 8p23.3 within the physical position 2.08 Mb from the 8p telomere. Chromosomal microarray analyses further assigned the duplication/deletion breakpoint at 2.16 Mb (Agilent 244K) and at 2.19 Mb (Affymetrix SNP6.0). Analysis of microsatellite DNA indicated that the psu idic(8)(p23.3) was derived from the maternal chromosome 8. Together, these findings indicate that the fetus was nullisomic for ∼2.2 Mb from 8pter, trisomic for the rest of chromosome 8 in mosaic condition, and likely had breaks in MYOM2 repeats of the maternal chromosome 8

Prenatal Diagnosis of Partial Trisomy 3p (3p21→pter) and Partial Monosomy 11q (11q23→qter) Associated with Abnormal Sonographic Findings of Holoprosencephaly, Orofacial Clefts, Pyelectasis and a Unilateral Duplex Renal System

Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21→pter) and partial monosomy 11q (11q23→qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23→qter) is associated with a duplex renal system

Cloning, Characterization, and FISH Mapping of Four Satellite DNAs from Black Muntjac ( Muntiacus crinifrons ) and Fea's Muntjac (M. feae)

Recent molecular cytogenetic studies demonstrate that extensive centromere-telomere fusions are the main chromosomal rearrangements underlying the karyotypic evolution of extant muntjacs. Although the molecular mechanism of tandem fusions remains unknown, satellite DNA is believed to have facilitated chromosome fusions by non-allelic homologous recombination. Previous studies detected non-random hybridization signals of cloned satellite DNA at the postulated fusion sites on the chromosomes in Indian and Chinese muntjacs. But the genomic distribution and organization of satellite DNAs in other muntjacs have not been investigated. In this study, we have isolated four satellite DNA clones (BMC5, BM700, BM1.1k and FM700) from the black muntjac ( Muntiacus crinifrons ) and Fea's muntjac (M. feae), and hybridized these four clones onto chromosomes of four muntjac species (M. reevesi, M. crinifrons, M. gongshanenisis and M. feae). Besides the predominant centromeric signals, non-random interstitial hybridization signals from satellite I and II DNA clones (BMC5, BM700 and FM700) were also observed on the arms of chromosomes of these four muntjacs. Our results provide additional support for the notion that the karyotypes of M. crinifrons, M. feae and M. gongshanensis have evolved from a 2n = 70 ancestral karyotype by a series of chromosome fusions

Chromosome 10q Deletion del (10)(q26.1q26.3) is Associated with Cataract

Distal 10q deletion syndrome is an uncommon chromosomal disorder. Interstitial deletion involving bands 10q25–10q26.1 is extremely rare and few cases have been reported. The characteristic features are facial dysmorphisms, postnatal growth retardation, developmental delay, congenital heart disease, genitourinary anomalies, digital anomalies, and strabismus. We report for the first time a patient with de novo 10q interstitial deletion del (10)(q26.1q26.3) and cataract

Sumoylation of p45/NF-E2: Nuclear Positioning and Transcriptional Activation of the Mammalian β-Like Globin Gene Locus

NF-E2 is a transcription activator for the regulation of a number of erythroid- and megakaryocytic lineage-specific genes. Here we present evidence that the large subunit of mammalian NF-E2, p45, is sumoylated in vivo in human erythroid K562 cells and in mouse fetal liver. By in vitro sumoylation reaction and DNA transfection experiments, we show that the sumoylation occurs at lysine 368 (K368) of human p45/NF-E2. Furthermore, p45 sumoylation enhances the transactivation capability of NF-E2, and this is accompanied by an increase of the NF-E2 DNA binding affinity. More interestingly, we have found that in K562 cells, the β-globin gene loci in the euchromatin regions are predominantly colocalized with the nuclear bodies promyelocytic leukemia protein (PML) oncogenic domains that are enriched with the PML, SUMO-1, RNA polymerase II, and sumoylatable p45/NF-E2. Chromatin immunoprecipitation assays further showed that the intact sumoylation site of p45/NF-E2 is required for its binding to the DNase I-hypersensitive sites of the β-globin locus control region. Finally, we demonstrated by stable transfection assay that only the wild-type p45, but not its mutant form p45 (K368R), could efficiently rescue β-globin gene expression in the p45-null, erythroid cell line CB3. These data together point to a model of mammalian β-like globin gene activation by sumoylated p45/NF-E2 in erythroid cells