Angelman Syndrome-Affected Individual with a Numerically Normal Karyotype and Isodisomic Paternal Uniparental Disomy of Chromosome 15 due to Maternal Robertsonian Translocation (14;15) by Monosomy Rescue

2018 ◽  
Vol 156 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Nuria C. Bramswig ◽  
Karin Buiting ◽  
Natalie Bechtel ◽  
Bernhard Horsthemke ◽  
Kevin Rostasy ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Robertsonian Translocation ◽  
Chromosome Region ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Normal Karyotype ◽  
Early Embryo ◽  
Affected Individual ◽  
Chromosome 15 ◽  
Paternal Uniparental Disomy

Angelman syndrome (AS) is a neurodevelopmental disorder caused by deletion of the maternally inherited 15q11q13 region, paternal uniparental disomy 15 [upd(15)pat], an imprinting defect of the maternal chromosome region 15q11q13, or a pathogenic mutation of the maternal UBE3A allele. Predisposing factors for upd(15)pat, such as nonhomologous robertsonian translocation involving chromosome 15, have been discussed, but no evidence for this predisposition has been published. In the present study, chromosomal analysis was performed in a child with AS, both parents, and the maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was employed on DNA of the index individual, and microsatellite analysis was carried out on DNA of the index individual and his parents. The cytogenetic analysis showed that the mother and maternal grandfather are carriers of a rob(14;15). The index individual has a numerically normal karyotype, but MS-MLPA and microsatellite analyses confirmed the clinical diagnosis of AS and revealed a pattern highly suggestive of isodisomic upd(15)pat. This is the first report of an AS-affected individual with isodisomic upd(15)pat and a numerically normal karyotype that most likely results from a rob(14;15)-associated meiotic error in the maternal germline followed by monosomy 15 rescue in the early embryo.

A Case of Angelman Syndrome Arising as a Result of a De Novo Robertsonian Translocation

1996 ◽  
Vol 45 (1-2) ◽  
pp. 255-261 ◽  
Author(s):  
S. Ramsden ◽  
L. Gaunt ◽  
A. Seres-Santamaria ◽  
J. Clayton-Smith
Keyword(s):  
Angelman Syndrome ◽  
Robertsonian Translocation ◽  
De Novo ◽  
Uniparental Disomy ◽  
Male Child ◽  
Paternal Uniparental Disomy

AbstractA male child has been identified with Angelman syndrome. He has been shown to carry a de novo Robertsonian 15/15 translocation where both chromosome 15s have been derived from the father. Consequently the disease in this instance is due to paternal uniparental disomy.

Paternal uniparental disomy of chromosome 15 in a child with angelman syndrome

1992 ◽  
Vol 32 (4) ◽  
pp. 512-518 ◽  
Author(s):  
Robert D. Nicholls ◽  
G. Shashidhar Pai ◽  
Wayne Gottlieb ◽  
Eduardo S. Cantú
Keyword(s):  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Paternal Uniparental Disomy

Angelman syndrome due to paternal uniparental disomy of chromosome 15: A milder phenotype?

1994 ◽  
Vol 51 (1) ◽  
pp. 35-40 ◽  
Author(s):  
A. Bottani ◽  
W. P. Robinson ◽  
C. D. Delozier-Blanchet ◽  
E. Engel ◽  
M. A. Morris ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Paternal Uniparental Disomy

Myoclonic status and central fever in Angelman syndrome due to paternal uniparental disomy

2015 ◽  
Vol 29 (4) ◽  
pp. 178-182
Author(s):  
Francesco Nicita ◽  
Giacomo Garone ◽  
Laura Papetti ◽  
Federica Consoli ◽  
Monia Magliozzi ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Paternal Uniparental Disomy

scholarly journals Quantitative Analysis of SRNPN Gene Methylation by Pyrosequencing as a Diagnostic Test for Prader–Willi Syndrome and Angelman Syndrome

2006 ◽  
Vol 52 (6) ◽  
pp. 1005-1013 ◽  
Author(s):  
Helen E White ◽  
Victoria J Durston ◽  
John F Harvey ◽  
Nicholas CP Cross
Keyword(s):  
Diagnostic Test ◽  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Small Nuclear Ribonucleoprotein ◽  
Maternal Contribution

Abstract Background: Angelman syndrome (AS) and Prader–Willi syndrome (PWS) are 2 distinct neurodevelopmental disorders caused primarily by deficiency of specific parental contributions at an imprinted domain within the chromosomal region 15q11.2-13. In most cases, lack of paternal contribution leads to PWS either by paternal deletion (∼70%) or maternal uniparental disomy (UPD; ∼30%). Most cases of AS result from the lack of a maternal contribution from this same region by maternal deletion (∼70%) or by paternal UPD (∼5%). Analysis of allelic methylation differences at the small nuclear ribonucleoprotein polypeptide N (SNRPN) locus can differentiate the maternally and paternally inherited chromosome 15 and can be used as a diagnostic test for AS and PWS. Methods: Sodium bisulfite–treated genomic DNA was PCR-amplified for the SNRPN gene. We used pyrosequencing to individually quantify the resulting artificial C/T sequence variation at CpG sites. Anonymized DNA samples from PWS patients (n = 40), AS patients (n = 31), and controls (n = 81) were analyzed in a blinded fashion with 2 PCR and 3 pyrosequencing reactions. We compared results from the pyrosequencing assays with those obtained with a commonly used methylation-specific PCR (MS-PCR) diagnostic protocol. Results: The pyrosequencing assays had a sensitivity and specificity of 100% and provided quantification of methylation at 12 CpG sites within the SNRPN locus. The resulting diagnoses were 100% concordant with those obtained from the MS-PCR protocol. Conclusions: Pyrosequencing is a rapid and robust method for quantitative methylation analysis of the SNRPN locus and can be used as a diagnostic test for PWS and AS.

Loss of Heterozygosity on the Distal Long Arm of Chromosome 15: An Allusion for Prader-willi Syndromes?

2021 ◽  
Author(s):  
Yang-Li Dai ◽  
Ke Huang ◽  
Ming-Qiang Zhu ◽  
Mian-Ling Zhong ◽  
Guan-Ping Dong ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Loss Of Heterozygosity ◽  
Critical Region ◽  
Neutral Loss ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Maternal Uniparental Disomy ◽  
Specific Pcr ◽  
Dependent Probe

Abstract BackgroundPrader-Willi syndrome (PWS) is a rare neurodevelopmental disorder that is partially caused by maternal uniparental disomy (UPD) of chromosome 15. Copy-neutral loss of heterozygosity (CN-LOH) observed on the distal long arm of chromosome 15 may be an indicator of UPD and may require additional genetic testing as chromosome 15 is known to harbor imprinted genes.MethodsChromosome microarray (CMA) was performed for two children with developmental disabilities or congenital anomalies. The results showed CN-LOH on the distal long arm of chromosome 15. Thereafter, methylation-specific PCR (MS-PCR) or methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis of PWS.ResultsMS-PCR did not detect an unmethylated allele for the SNRPN gene or MS-MLPA hypermethylation in 15q11.2-q13.1 region, supporting the diagnosis of PWS.ConclusionsThese data suggested that LOH on chromosome 15, and even the critical region of 15q11.2q13.1 was not involved, perhaps due to partial heterodisomy and partial isodisomy UPD15. Hence, other genetic tests are warranted for the diagnosis of PWS.

scholarly journals Clinical-neurologic, cytogenetic and molecular aspects of the Prader-Willi and Angelman Syndromes

1997 ◽  
Vol 55 (2) ◽  
pp. 199-208 ◽  
Author(s):  
João M. de Pina-Neto ◽  
Victor Evangelista F. Ferraz ◽  
Greice Andreotti de Molfetta ◽  
Jess Buxton ◽  
Sarah Richards ◽  
...  
Keyword(s):  
De Novo ◽  
Cpg Island ◽  
Chromosome Region ◽  
Uniparental Disomy ◽  
Restriction Enzymes ◽  
University Hospital ◽  
Chromosome 15 ◽  
Maternal Chromosome ◽  
Conventional Cytogenetics ◽  
Cytogenetical Analysis

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are human neurogenetic disorders involving the imprinting mechanism, at the 15q11-13 chromosome region. The predominant genetic defects in PW are 15q 11-13 deletions of paternal origin and maternal chromosome 15 uniparental disomy. In contrast, maternal deletions and paternal chromosome 15 uniparental disomy are associated with a different neurogenetic disorder, the AS. In both disorders, these mutations are associated with parent-of-origin specific methylation at several 15q 11-13 loci. We studied 5 patients suspect of PWS and 4 patients suspect of AS who were referred to the Medical Genetics Unit at the University Hospital of Medical School from Ribeirão Preto. Our objective was to establish the correct clinical and etiological diagnosis in these cases. We used conventional cytogenetics, methylation analysis with the probe KB 17 (CpG island of the SNRPN gene) by Southern blotting after digestion with the Xba I and Not I restriction enzymes. We studied in patients and their parents the segregation of the (CA)n repeats polymorphisms by PCR, using the primers 196 and IR4-3R. All the patients had normal conventional cytogenetical analysis. We confirmed 3 cases of PWS: one by de novo deletion, one by maternal chromosome 15 uniparental disomy and one case with no defined cause determined by the used primers. We confirmed 2 cases of AS, caused by de novo deletion at the 15q 11-13 region, and one case with normal molecular analysis but with strong clinical characteristics.

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