Further patient with Angelman syndrome due to paternal disomy of chromosome 15 and a milder phenotype

1995 ◽  
Vol 56 (3) ◽  
pp. 328-329 ◽  
Author(s):  
Gabriele Gillessen-Kaesbach ◽  
Beate Albrecht ◽  
Eberhard Passarge ◽  
Bernhard Horsthemke
Keyword(s):  
Angelman Syndrome ◽  
Chromosome 15

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.

scholarly journals A Streamlined Approach to Prader-Willi and Angelman Syndrome Molecular Diagnostics

2021 ◽  
Vol 12 ◽  
Author(s):  
Samuel P. Strom ◽  
Waheeda A. Hossain ◽  
Melina Grigorian ◽  
Mickey Li ◽  
Joseph Fierro ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Genetic Defect ◽  
Point Mutations ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Disease Diagnosis ◽  
Genetic Alterations ◽  
Chromosome 15 ◽  
Current Standard ◽  
Care Technology

Establishing or ruling out a molecular diagnosis of Prader–Willi or Angelman syndrome (PWS/AS) presents unique challenges due to the variety of different genetic alterations that can lead to these conditions. Point mutations, copy number changes, uniparental isodisomy (i-UPD) 15 of two subclasses (segmental or total isodisomy), uniparental heterodisomy (h-UPD), and defects in the chromosome 15 imprinting center can all cause PWS/AS. Here, we outline a combined approach using whole-exome sequencing (WES) and DNA methylation data with methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) to establish both the disease diagnosis and the mechanism of disease with high sensitivity using current standard of care technology and improved efficiency compared to serial methods. The authors encourage the use of this approach in the clinical setting to confirm and establish the diagnosis and genetic defect which may account for the secondary genetic conditions that may be seen in those with isodisomy 15, impacting surveillance and counseling with more accurate recurrence risks. Other similarly affected individuals due to other gene disorders or cytogenetic anomalies such as Rett syndrome or microdeletions would also be identified with this streamlined approach.

Blended phenotype of AP4E1 deficiency and Angelman syndrome caused by paternal isodisomy of chromosome 15

2020 ◽  
Vol 42 (3) ◽  
pp. 289-292 ◽  
Author(s):  
Hiroaki Murakami ◽  
Tomoko Uehara ◽  
Yoshinori Tsurusaki ◽  
Yumi Enomoto ◽  
Yukiko Kuroda ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Chromosome 15

Molecular Analysis of an Extra inv dup(15)(q13) Chromosome in Two Patients with Angelman Syndrome

1996 ◽  
Vol 45 (1-2) ◽  
pp. 217-220 ◽  
Author(s):  
T. Buchholz ◽  
S. Schuffenhauer ◽  
K. Evans ◽  
L. Robson ◽  
B. Appleton ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Angelman Syndrome ◽  
Uniparental Disomy ◽  
Molecular Data ◽  
Monoallelic Expression ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Loss Of Function ◽  
Maternal Allele ◽  
Molecular Defects

Angelman syndrome (AS) is caused by the loss of function of yet unidentified gene(s) which map within 15q 11-13 and show monoallelic expression from the maternal allele. Lack of the maternal allele(s), due to either a deletion on the maternal chromosome 15 (about 70% of AS patients) or a paternal uniparental disomy (UPD)15 (<5%), are the most common molecular defects in AS. Prader-Willi syndrome (PWS) also maps to proximal 15q, but is caused by the loss of function of paternally expressed gen(s) [1]. Here we describe clinical, cytogenetic and molecular data for two non-related patients with AS who carry a nonmosaic extra cromosome inv dup(15).

scholarly journals A Case of Fundus Oculi Albinoticus Diagnosed as Angelman Syndrome by Genetic Testing

2018 ◽  
Vol 9 (1) ◽  
pp. 108-113 ◽  
Author(s):  
Yurie Fukiyama ◽  
Masahiro Tonari ◽  
Junko Matsuo ◽  
Hidehiro Oku ◽  
Jun Sugasawa ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Visual Tracking ◽  
Angelman Syndrome ◽  
Optic Atrophy ◽  
Chromosome 15 ◽  
Complete Physical Examination ◽  
Respiratory Disturbance ◽  
Testing Case ◽  
Fundus Oculi

Purpose: To report a case of fundus oculi albinoticus diagnosed as Angelman syndrome (AS) via genetic testing. Case Report: This study reports on a 4-year-old boy. Since he had been having respiratory disturbance since birth, he underwent a complete physical examination to investigate the cause. The results indicated that he had various brain congenital abnormalities, such as a thin corpus callosum, as well as hydronephrosis, an atrial septal defect, and skin similar to patients with fundus oculi albinoticus. Examination revealed bilateral fundus oculi albinoticus, mild iridic hypopigmentation, optic atrophy, and poor visual tracking. Genetic testing revealed a deletion in the Prader-Willi syndrome/AS region on chromosome 15, and together with the results of methylation analysis, his condition was diagnosed as AS. Follow-up examinations revealed no change in the fundus oculi albinoticus and optic atrophy, nor did they indicate poor visual tracking. Conclusions: When fundus oculi albinoticus and optic atrophy are observed in patients with multiple malformations, AS should be considered as a differential diagnosis.

scholarly journals Common genetic variation in the Angelman syndrome imprinting centre affects the imprinting of chromosome 15

2020 ◽  
Vol 28 (6) ◽  
pp. 835-839
Author(s):  
Jasmin Beygo ◽  
Christian Grosser ◽  
Sabine Kaya ◽  
Claudia Mertel ◽  
Karin Buiting ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Angelman Syndrome ◽  
Chromosome 15 ◽  
Common Genetic Variation

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.

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