Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Uniparental Disomy”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1997

Comparison of phenotype between patients with Prader-Willi syndrome due to deletion 15q and uniparental disomy 15.

Prader-Willi syndrome (PWS) is a complex multiple anomaly syndrome that has been shown to result from deficient expression of paternal chromosome 15(q11-q13). In most cases, it is caused either by deletion of this region in the paternally inherited chromosome 15 or by maternal uniparental disomy (UPD) of chromosome 15. In order to determine whether there are phenotypic differences between patients whose PWS is caused by these two different mechanisms, 54 affected individuals (37 with deletion, 17 with UPD) were personally examined and studied using molecular techniques. The previously recognized increased maternal age in patients with UPD and increased frequency of hypopigmentation in those with deletion were confirmed. Although the frequency and severity of most other manifestations of PWS did not differ significantly between the two groups, those with UPD were less likely to have a "typical" facial appearance. In addition, this group was less likely to show some of the minor manifestations such as skin picking, skill with jigsaw puzzles, and high pain threshold. Females and those with UPD were also older, on average. Possible mechanisms by which these differences could occur and the implications of these differences for diagnosis are described.

Adolescent↗
PubMed1996

Why is there no diploid overdose effect in Prader-Willi syndrome due to uniparental disomy?

Due to DNA technology, it is now apparent that the mechanisms of genetic disease are more complex than the model of a gene with biallelic expression in the diploid state. If a gene is imprinted, monoallelic expression is the norm when the chromosomes of a pair are inherited normally from each parent. Uniparental disomy (UPD) is the abnormal situation where both chromosomes of a pair come from the same parent. When the chromosome contains an imprinted gene, UPD may result in nullisomy or disomy for a functional copy of that gene. If there are two imprinted loci on the same chromosome, UPD for that chromosome results in nullisomy for one imprinted gene but functional disomy for the other a "diploid overdose" (DO). This situation has been well demonstrated in the Prader-Willi syndrome (PWS) which is the nullisomic phenotype for the PWS gene(s) on chromosome 15q11-13. Chromosome 15q11-13 also contains the gene for Angelman syndrome (AS) which has a phenotype distinct from PWS. Both loci are subject to imprinting--in PWS, the imprint is on the maternal chromosome 15, in AS it is on the paternal chromosome 15. All individuals with PWS due to maternal UPD, while functionally nullisomic for the PWS locus, are functionally disomic for the AS locus--a DO situation. Assuming that biallelic expression of an imprinted gene is harmful, one would expect DO for an imprinted gene to produce a phenotypic effect. Cases of PWS due to UPD do not appear to differ from those due to deletion (hypopigmentation in deletional cases can be explained by loss of D15S12 downstream from the critical region). There is no good evidence of DO for the AS locus in PWS due to UPD. Why then was it 'necessary' in evolutionary terms to imprint the AS locus and maintain the imprint faithfully for life. A similar situation of two imprinted genes on the same chromosome occurs with IGF2 and H19 on chromosome 11p15. Maternal imprinting for IGF2 and paternal imprinting for H19 is the norm. Paternal UPD in this situation does lead to a DO effect, namely Beckwith-Wiedemann syndrome. The possibility of a DO effect needs to be considered when assessing the phenotypic spectrum of UPD for other chromosomes currently under investigation.

Animals↗
PubMed1997

Meiotic origin of trisomy in confined placental mosaicism is correlated with presence of fetal uniparental disomy, high levels of trisomy in trophoblast, and increased risk of fetal intrauterine growth restriction.

Molecular studies were performed on 101 cases of confined placental mosaicism (CPM) involving autosomal trisomy. The origin of the trisomic cell line was determined in 54 cases (from 51 pregnancies), 47 of which were also analyzed for the presence of uniparental disomy (UPD) in the disomic cell line. An additional 47 cases were analyzed for parental origin in the disomic cell line only. A somatic (postmeiotic) origin of the trisomy was observed in 22 cases and included the majority of cases with CPM for trisomy 2, 7, 8, 10, and 12. Most cases of CPM involving trisomy 9, 16, and 22 were determined to be meiotic. Fetal maternal UPD was found in 17 of 94 informative CPM cases, involving trisomy 2 (1 case), 7 (1 case), 16 (13 cases), and 22 (2 cases). The placental trisomy was of meiotic origin in all 17 cases associated with fetal UPD (P = .00005). A meiotic origin also correlated with the levels of trisomy in cultured chorionic villi samples (CVS) (P = .0002) and trophoblast (P = .00005). Abnormal pregnancy outcome (usually IUGR) correlated with meiotic origin (P = .0003), the presence of fetal UPD (P = 4 x 10(-7)), and the level of trisomy in trophoblast (P = 3 x 10(-7)) but not with the level of trisomy in CVS or term chorion. The good fit of somatic errors with the expected results could have been observed only if few true meiotic errors were misclassified by these methods as a somatic error. These data indicate that molecular determination of origin is a useful predictor of pregnancy outcome, whereas the level of trisomy observed in cultured CVS is not. In addition, UPD for some chromosomes may affect prenatal, but not postnatal, development, possibly indicating that imprinting effects for these chromosomes are confined to placental tissues.

Cells, Cultured↗
PubMedDate not supplied

Sporadic occurrence of nondeletion Prader-Willi syndrome in two cases: a female with maternal uniparental disomy and a male with complex chromosomal rearrangement.

We report here two cases of nondeletion Prader-Willi syndrome (PWS). Case 1 is a 9-yr-old female patient with classical features of the syndrome and cytogenetically normal chromosome 15. DNA analysis using polymorphic probes for Prader-Willi Critical Region (PWCR) showed absence of paternal alleles while maternal uniparental isodisomy (UPisoD) was confirmed. This is the first report of nondeletion PWS with uniparental disomy (UPD) in the population of Kuwait. The second case with Prader-Willi syndrome-like features had normal chromosome 15 but showed familial complex chromosomal rearrangement (CCR) involving chromosomes 13, 19, and 20 inherited from his mother. No paternal deletion or UPD disomy was observed after DNA molecular analysis. This is a case of "atypical" PWS with no cytogenetic or molecular abnormality for PWCR. The two cases represent two different mechanisms associated with nondeletion PWS.

Alleles↗
PubMed1993

Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome.

Chromosome 15 (15q11-q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation.

Angelman Syndrome↗
PubMed1994

Bloom syndrome and maternal uniparental disomy for chromosome 15.

Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions.

Bloom Syndrome↗
PubMed1991

Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome.

Six Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likelihood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.

Blotting, Southern↗
PubMed1996

Maternal uniparental disomy for chromosome 2 in association with confined placental mosaicism for trisomy 2 and severe intrauterine growth retardation.

We report a liveborn infant with severe intrauterine growth retardation and renal failure, delivered following detection of non-mosaic trisomy 2 by chorionic villus biopsy in the first trimester. Detailed analysis post-delivery indicated apparent complete trisomy 2 of the chorionic tissues, with a chromosomally normal infant demonstrating maternal uniparental disomy for chromosome 2.

Adult↗
PubMed1993

Uniparental disomy explains the occurrence of the Angelman or Prader-Willi syndrome in patients with an additional small inv dup(15) chromosome.

A patient with Angelman syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q11: q11-->pter) karyotype and a patient with Prader-Willi syndrome and a 46,XY/47,XY,+inv dup(15)(pter-->q12: q12-->pter) karyotype were investigated with molecular markers along chromosome 15. Paternal uniparental isodisomy was found for all informative markers in the first case which indicates that this, rather than the presence of the extra chromosome, is the cause of the Angelman syndrome phenotype. Similarly, the PWS patient showed maternal uniparental distomy with absence of PWS region material on the inv dup(15) chromosome. If (1) marker chromosomes are an occasional by product of 'rescuing' a trisomic fertilisation, or (2) if duplication of the normal homologue in a zygote which has inherited a marker in place of the normal corresponding chromosome 'rescues' an aneuploid fertilisation, or (3) if the presence or formation of a marker chromosome increases the probability of non-disjunction, then uniparental disomy might be found occasionally in other subjects with de novo marker chromosomes.

Angelman Syndrome↗
PubMed1994

Chromosome 14 maternal uniparental disomy in the euploid cell line of a fetus with mosaic 46,XX/47,XX,+14 karyotype.

We investigated the parental origin of the extra chromosome 14 and of the two chromosomes 14 of the euploid cell line, in a case of fetal mosaicism 46,XX/47,XX+14 diagnosed at amniocentesis. Molecular analysis of five polymorphic loci of the short tandem repeat type was performed. Markers D14S43 and D14S49 showed the presence of maternal uniparental disomy of chromosome 14 in the apparently normal cell line. The distribution of the markers analysed along the chromosome suggests maternal heterodisomy with a large isodisomic segment in the telomeric region, possibly caused by meiotic crossing-over.

Adult↗
PubMed1992

Paternal uniparental disomy of chromosome 15 in a child with Angelman syndrome.

Angelman and Prader-Willi syndromes are clinically distinct neurobehavioral disorders most commonly resulting from large deletions of chromosome 15q11-q13. The deletions arise differentially during maternal or paternal gametogenesis, respectively. A subgroup of patients with either syndrome have no apparent deletion, and because many such patients with Prader-Willi syndrome display inheritance of two copies of chromosome 15 from the mother only (uniparental disomy; UPD), we suggested that paternal UPD might be found in patients with Angelman syndrome. We report here clinical, cytogenetic, and molecular evidence on the 1 patient with paternal UPD for chromosome 15 who was found in our study population. This represents, to our knowledge, the first patient with paternal UPD to be studied with DNA probes from the chromosome 15q11-q13 critical region. In contrast to our findings for patients with Prader-Willi syndrome, in which maternal UPD was common, our data demonstrate that paternal UPD is infrequent in patients with Angelman syndrome.

Angelman Syndrome↗
PubMed1997

Maternal uniparental disomy 7 in Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is characterised by intrauterine and postnatal growth failure accompanied by a variable number of dysmorphic features. It is usually sporadic although a few familial cases have been described. In a prospective study of 33 patients with sporadic SRS, we have studied the parent of origin of chromosome 7 using variable number tandem repeat (VNTR) or microsatellite repeat markers and have identified two patients with maternal uniparental disomy of chromosome 7 (mUPD7). In one family, inconsistent inheritance of paternal alleles of markers on chromosomes other than 7 led to their exclusion from further study. The probands were clinically mild and symmetrical, but showed no gross clinical differences from the 30 patients with chromosome 7 derived from both parents.

Abnormalities, Multiple↗
PubMedDate not supplied

Beckwith-Wiedemann syndrome-associated hepatoblastoma: wnt signal activation occurs later in tumorigenesis in patients with 11p15.5 uniparental disomy.

Beckwith-Wiedemann syndrome (BWS) patients with chromosome 11p15.5 uniparental isodisomy (UPD) have an increased risk for developing embryonal tumors. UPD in these patients involves maternal loss of heterozygosity (LOH) and paternal duplication, which leads to tissue overgrowth and tumor development. Although 11p15.5 UPD predisposes to tumorigenesis, the events leading to tumorigenesis in UPD patients remains unknown. We have examined two hepatoblastomas in the BWS patients with UPD to determine the sequence of genetic events. Constitutional 11p15.5 LOH was detected in the blood or nonneoplastic liver of the BWS patients with hepatoblastoma. Mutation of beta-catenin gene (CTNNB1) was found in one hepatoblastoma. Although mutations in CTNNB1 were not found in the second hepatoblastoma, nuclear accumulation of beta-catenin was detected. However, mutation of CTNNB1 or nuclear accumulation of beta-catenin was not detected in the tissue with hepatomegaly which contains UPD cells. These data indicate that Wnt signal activation can be involved as a later event in BWS-associated hepatoblastoma involving 11p15.5 UPD.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Maternal uniparental disomy for chromosome 14.

A girl carrying a de novo balanced 13-14 robertsonian translocation showed a clinical phenotype with severe hypotonia, hyperextensible joints, frontal bossing, asymmetric face, no mental retardation, severe scoliosis and motor delay. In situ hybridization analysis on chromosome spreads revealed the presence of the two centromeres in the rearranged chromosomes. Molecular analysis on genomic DNA showed the presence in the proposita of two chromosomes 14 of maternal origin and no chromosome 14 from the father indicating a maternal monocentric uniparental disomy for chromosome 14 (mUPD14). Our patient shows several similarities with other reported cases of mUPD14, suggesting imprinting of a region(s) of chromosome 14 and defining a possible mUPD14 Syndrome.

Chromosome Aberrations↗
PubMed1994

Mosaic uniparental disomy in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with variable expression. The major features are anterior abdominal wall defects, macroglossia, and gigantism and less commonly neonatal hypoglycaemia, organomegaly, congenital renal anomalies, hemihypertrophy and embryonal tumours occur. BWS is a genetically heterogeneous disorder; most cases are sporadic but approximately 15% are familial and a small number of BWS patients have cytogenetic abnormalities involving chromosome 11p15. Genomic imprinting effects have been implicated in familial and non-familial BWS, and uniparental disomy (UPD) for chromosome 11 has been reported in sporadic cases. We investigated the incidence, pathogenesis, and clinical associations of UPD in 49 patients with non-familial BWS and a normal karyotype. UPD for chromosome 11p15 was detected in nine of 32 (28%) informative patients. A further two patients appeared to be disomic at the WT1 locus in chromosome 11p13, but were uninformative at chromosome 11p15.5 loci tested. In all cases with UPD the affected person was mosaic for a paternal isodisomy and a normal cell line indicating that UPD had arisen as a postzygotic event. Compared to cases in which paternal isodisomy for chromosomes 11p15.5 had been excluded (n = 23), BWS patients with UPD was more likely to have hemihypertrophy (6/9 versus 1/23, p < 0.001) and less likely to have exomphalos (0/9 versus 13/23, p < 0.01), but there were no significant differences between disomic and non-disomic cases in the incidence of hypoglycaemia, nephromegaly, neoplasia, and developmental delay. The detection of UPD in BWS patients allows accurate genetic counselling to be provided and provides an insight into the molecular pathogenesis of BWS.

Adolescent↗
PubMed1994

Maternal uniparental disomy 22 has no impact on the phenotype.

A 25-year-old normal healthy male was karyotyped because five of his wife's pregnancies terminated in spontaneous abortions at 6-14 wk of gestation. Cytogenetic investigation disclosed a de novo balanced Robertsonian t(22q;22q) translocation. Molecular studies revealed maternal only inheritance for chromosome 22 markers. Reduction to homozygosity for all informative markers indicates that the rearranged chromosome is an isochromosome derived from one of the maternal chromosomes 22. Except for the possibility of homozygosity for recessive mutations, maternal uniparental disomy 22 does not seem to have an adverse impact on the phenotype, apart from causing reproductive failure. It can be concluded that no maternally imprinted genes with major effect map to chromosome 22.

Abortion, Spontaneous↗
PubMedDate not supplied

Trisomy first, translocation second, uniparental disomy and partial trisomy third: a new mechanism for complex chromosomal aneuploidy.

A 2-year-old, short, microcephalic and developmentally retarded boy revealed a pattern of multiple minor anomalies, hypospadias and a dysplastic right kidney. Maternal age at delivery was 41 years. His karyotype showed two cell lines, one apparently normal, the other with a 1p+ chromosome. FISH examinations showed that the segment attached to 1p was from chromosome 16, and molecular investigations disclosed maternal heterodisomy 16, except for the segment (16)(pter-->p13.1) for which there was mosaicism between trisomy and uniparental disomy (UPD). Most likely, the zygote was trisomic for chromosome 16 due to a maternal meiosis I nondisjunction; a somatic rearrangement would have then occurred at an early postzygotic stage whereby a segment of the paternal chromosome 16 was translocated onto 1p. Subsequently, the paternal chromosomes 16 and 16p- had been lost in the normal and the translocation cell line, respectively. The chromosome aberration was detected secondary to the disclosure of maternal UPD 16 because of the demonstration of a paternal band at several loci on distal 16p. This case shows that chromosome aberrations may be formed in a more complicated manner than primarily assumed. Hence, the phenotype might also be due to underlying factors such as UPD or undetected mosaicism in addition to the more obvious implications of the chromosome rearrangement itself (e.g. partial trisomy).

Abnormalities, Multiple↗
PubMed1998

Unusual clinical features in an Angelman syndrome patient with uniparental disomy due to a translocation 15q15q.

We had previously described a patient with an overgrowth syndrome and the chromosome constitution 45,XY,t(15q15q) (Wajntal et al., DNA Cell Biol 1993: 12: 227-231). Clinical reassessment and the use of molecular studies, including methylation analysis with an SNRPN probe, microsatellite analyses of D15S11, GABRB3 and D15S113 loci, and fluorescence in situ hybridization (FISH) using the SNRPN and GABRB3 probes, are consistent with a diagnosis of Angelman syndrome (AS) due to paternal isodisomy. This is the fourth report case of a translocation 15q15q with paternal uniparental disomy (UPD). Our findings suggest that some patients with clinical features of AS have hyperphagia and obesity with overgrowth, and that these features should not rule out a diagnosis of AS.

Angelman Syndrome↗