1/9. Two cases of mosaic RhD blood-group phenotypes and paternal isodisomy for chromosome 1.We encountered a 22-year-old man (case 1) and a 23-year-old woman (case 2), both unrelated and healthy. They were mosaic for the Rh blood group phenotype: one erythrocyte population was D-positive and the other was D-negative. Flow cytometric analysis of density profile of RhD antigen in their erythrocytes, and cytogenetic analysis including in situ hybridization using an RHD/RHCE-containing PAC clone, excluded a deletion of the RHD/RHCE gene complex, but suggested the presence of cells with uniparental disomy for chromosome 1 (UPD1). Microsatellite marker analysis was performed in both probands and their family members. In case 1, the analysis with markers spanning the chromosome 1 revealed both maternal and paternal alleles in his peripheral blood leukocytes (PBL), Epstein-Barr virus-transformed lymphoblastoid cells (EBL), and buccal mucosal cells. However, only paternal alleles were detected in all of 50 individual pieces of his hair or hair-roots and all of five monoclonal cell lines cloned from his established EBL. There was no direct evidence of heterozygous, biparental alleles in these two tissues. The presence of maternal isodisomy 1 was not absolutely ruled out in other tissues examined in case 1. Similar results were obtained in case 2, showing biparental, disomic patterns in her PBL and in 15 of 20 pieces of her hair roots, and showing monoallelic patterns in the remaining five pieces of hair roots. Analysis with markers for other autosomes confirmed their biparental inheritance. These findings indicated that both cases had at least two cell populations, one population having paternal UPD1 (isodisomy 1), and another heterozygous, biparental disomy 1. We emphasize that isodisomy for chromosome 1 is not infrequent and may cause unusual RhD phenotype, as seen in cases we described.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/9. Maternal uniparental isodisomy 10 and mosaicism for an additional marker chromosome derived from the paternal chromosome 10 in a fetus.We report a case of maternal isodisomy 10 combined with mosaic partial trisomy 10 (p12.31-q11.1). Chromosome examinations from a CVS sample showed a karyotype 47,XX, mar/46,XX [corrected]. The additional marker chromosome which was present in 6/25 interphase nuclei was shown by fluorescence in situ hybridization (FISH) to have been derived from a pericentromeric segment of chromosome 10. dna analysis was performed from umbilical cord blood from the fetus after termination of the pregnancy at 18 weeks. The results showed that the two structurally normal chromosomes 10 were both of maternal origin, whereas the marker chromosome derived from the father. autopsy of the fetus revealed hypoplasia of heart, liver, kidneys and suprarenal glands, but, apart from a right bifid ureter, no structural organ abnormalities. This fetus represents the second reported instance of a maternal uniparental disomy (UPD) 10.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/9. Maternal isodisomy for 14q21-q24 in a man with diabetes mellitus.We report a 20-year-old man with maternal uniparental disomy for chromosome 14 (UPD14) and maturity-onset diabetes mellitus (DM). He had pre- and postnatal growth retardation, developed DM at age 20 years without any autoimmune antibodies, and had a mosaic 45,XY,der(14;14)(q10;q10)[129]/46,XY, 14,der(14;14)(q10;q10)[1] karyotype. Allelotyping using microsatellite markers covering the entire 14q indicated segmental maternal isodisomy for 14q21-q24 and maternal heterodisomy of the remaining regions of the chromosome. It is thus tempting to speculate that the segmental isodisomy led to reduction to homozygosity for a mutant gene and thus caused his DM, although the possibility of coincidental occurrence of the two events cannot totally be ruled out. fluorescence in situ hybridization (FISH) analysis using BAC clone probes revealed that the isodisomic segment did not overlap any known IDDM or NIDDM susceptibility loci on chromosome 14, suggesting a novel locus for a subset of DM at the isodisomic segment.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/9. First patient with trisomy 21 accompanied by an additional der(4)(:p11 --> q11:) plus partial uniparental disomy 4p15-16.We report on a rare additional numerical chromosomal aberration in a child with down syndrome due to free trisomy 21. The karyotype showed 48,XY, 21, mar after GTG banding, with the marker present in 80% of cells. The supernumerary marker chromosome (SMC) was as small as approximately one-third of 18p, and with the recently developed centromere-specific multi-color fluorescence in situ hybridization (cenM-FISH) technique, it was shown that the SMC was a derivative chromosome 4. The SMC was not specifically stained by arm-specific probes for chromosome 4; thus, it has been described as der(4)(:p11 --> q11:). Microsatellite analysis resulted in a partial maternal uniparental isodisomy (UPD) for chromosome 4p15-16 and a maternal origin for two chromosomes 21. Until now only two similar cases have been described in the literature, but without clarifying the origin of the SMC and without looking for an additional UPD. This is the only reported case of a UPD 4p in a liveborn child.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/9. Maternal uniparental disomy in a patient with prader-willi syndrome with an additional small inv dup(15) chromosome.prader-willi syndrome (PWS) is a complex genetic disorder. About 70% of cases have a paternal deletion at 15q11-q13, and most of the remaining cases are caused by maternal uniparental disomy (UPD). In rare cases of PWS with maternal UPD, small marker chromosomes are identified. patients with inv dup(15) are at an increased risk of developing PWS or angelman syndrome (AS) due to UPD. They may be also at increased risk for developmental delay due to additional copies of genes located within the PWS/AS critical region. Therefore, molecular investigations in patients with a supernumerary marker chromosome (SMC) are necessary to provide proper genetic counseling. We report a female infant with central hypotonia, weak crying, feeding problems, failure to thrive, and developmental delay after birth. Chromosome analysis revealed an SMC in 55% of metaphase cells. fluorescence in situ hybridization showed that this marker chromosome was constituted by a small isodicentric inverted duplication of chromosome 15 [inv dup(15)]. Microsatellite analysis showed uniparental isodisomy of maternal chromosome 15 in the proband. diagnosis of PWS was further confirmed by methylation-specific polymerase chain reaction. The inv dup(15) marker chromosome was also of maternal origin. Follow-up at the age of 18 months revealed a height in the 10th percentile and weight in the 50th percentile. She had poor activity and muscle tone, and was unable to walk independently. There was no psychomotor retardation, behavior disturbance or seizure.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/9. Another small supernumerary marker chromosome (sSMC) derived from chromosome 2: towards a genotype/phenotype correlation.Here we report a prenatally detected small supernumerary marker chromosome (sSMC) derived from chromosome 2 as demonstrated by cenM-FISH (centromere-specific multicolor fluorescence in situ hybridization). By application of a recently described subcentromere-specific probe set (subcenM-FISH) for chromosome 2, the presence of a small partial trisomy due to a karyotype 47,XX, r(2)(::p11.1->q11.2::) was demonstrated. Including this case, a total of 11 patients with sSMC(2) are described throughout the literature. Based on that data, a first genotype/phenotype correlation according to the size and structure of the marker is suggested.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/9. Forty-two supernumerary marker chromosomes (SMCs) in 43,273 prenatal samples: chromosomal distribution, clinical findings, and UPD studies.fluorescence in situ hybridization (FISH) analyses were performed on supernumerary marker chromosomes (SMCs) detected in 43,273 prenatal diagnoses over a period of 11 years, 1993-2003. A total of 42 pregnancies with SMC were identified, indicating a prevalence of one in 1032. A total of 15 SMCs were endowed with detectable euchromatin (prevalence, 1/2884), including six SMCs containing the cat eye critical region (CECR) on chromosome 22q11.21 (1/7212). De novo SMCs were found in 29 pregnancies (1/1492), including 14 euchromatic SMCs (48.2%). follow-up studies were available for 24 cases. Nine pregnancies (37.5%) were terminated; two children (8.3%) were born with Pallister-Killian syndrome and cat eye syndrome (CES), respectively; 13 children (54.1%) showed apparently normal development. Familial SMCs were identified in 13 pregnancies (1/3328) from 11 unrelated women. They were all acrocentric. In all, 10 were heterochromatic and one was an extra der(22)t(11;22) chromosome. A total of 12 cases were available for follow-up. One pregnancy was terminated due to anhydramnios, spina bifida, and cystic-dysplastic kidneys; one child suffered from a der(22) syndrome; 10 children (83.3%) appeared unaffected. Studies for uniparental disomy were performed on seven pregnancies and revealed a case of maternal heterodisomy for chromosome 22. So far this is the largest FISH study of prenatally ascertained SMCs and the first study with detailed data on the prevalence. Findings illustrate the spectrum and clinical outcomes of prenatally diagnosed SMCs, and indicate a higher frequency of SMCs than generally assumed.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/9. Supernumerary marker chromosome 7 and maternal uniparental disomy 7 in a boy with growth retardation and triangular face.We report on a 12-month-old boy with pre and post-natal growth retardation, triangular face and mild psychomotor retardation. karyotyping revealed a supernumerary marker chromosome (SMC) in 36% of cells. Using fluorescence in situ hybridization and BAC clones, the supernumerary marker chromosome was found to be a highly deleted chromosome 7 with breakpoints within the pericentric euchromatin (partial trisomy 7). Microsatellite typing indicated maternal uniparental disomy of chromosome 7 (matUPD7). The patient showed only few signs of the silver-russell syndrome. He therefore reflects the mild end of the phenotypic spectrum in patients with matUPD7. The case supports the argument that karyotyping is warranted in patients with short stature and only few additional features, and that UPD studies are required in patients with a SMC(7). Considering that the SMC(7) contributed very little, if any, to the phenotype of this boy, we propose that UPD7 studies should be carried out in children with pre- and postnatal growth retardation of unknown cause even in the absence of a SMC.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/9. Mosaic maternal uniparental isodisomy for chromosome 7q21-qter.uniparental disomy (UPD) for several human chromosomes is associated with clinical abnormalities. We report the case of a 2-year-old boy with severe intrauterine and post-natal growth retardation (IUGR/PNGR) and highly variable sweat chloride concentrations. The patient was identified as heterozygous for the F508del mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Unexpectedly, the signal corresponding to the maternally inherited F508del allele appeared much more intense than the paternally derived wild allele. Molecular analysis including polymorphic marker studies, microsatellites and single-nucleotide polymorphisms subsequently showed that the boy was a carrier of a de novo mosaic maternal isodisomy of a chromosome 7 segment while there was a biparental inheritance of the rest of the chromosome. This is the first report of a mosaic partial UPD7. The matUPD7 segment at 7q21-qter extends for 72.7 Mb. The karyotype (550 bands) of our patient was normal, and fluorescence in situ hybridization with probes mapping around the CFTR gene allowed us to rule out a partial duplication. The detection of this chromosomal rearrangement confirms the hypothesis that the 7q31-qter segment is a candidate for the localization of human imprinted genes involved in the control of IUGR and PNGR. It also emphasizes the importance of searching for UPD7 in severe, isolated and unexplained IUGR and PNGR.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |