Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15 in a boy with a balanced 3;21 translocation

2001 ◽  
Vol 100 (1) ◽  
pp. 85-86 ◽  
Author(s):  
Lori L. Bassett ◽  
Ron C. Michaelis ◽  
Mary Holland Geiger ◽  
Jack Tarleton ◽  
C. Lynn Moore ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy

Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study

2019 ◽  
Vol 32 (8) ◽  
pp. 879-884 ◽  
Author(s):  
Raquel Corripio ◽  
Carla Tubau ◽  
Laura Calvo ◽  
Carme Brun ◽  
Núria Capdevila ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Prospective Study ◽  
Mixed Model ◽  
Standard Deviation Score ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Maternal Uniparental Disomy ◽  
A Prospective Study

Abstract Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0–18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p < 0.001) in tricipital and subcapsular skinfold thickness, with an upward trend of height SDS and a downward trend of BMI SDS, was observed. Infants who started GH before 15 months of age started walking at a median of 18.0 [17.0–19.5] months vs. 36.6 [36.3–37.8] months for those who began treatment with GH after 15 months of age (p = 0.024). Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.

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.

Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: Utility of genome-wide SNP array

2012 ◽  
Vol 161 (1) ◽  
pp. 166-171 ◽  
Author(s):  
Kosuke Izumi ◽  
Avni B. Santani ◽  
Matthew A. Deardorff ◽  
Holly A. Feret ◽  
Tanya Tischler ◽  
...  
Keyword(s):  
Snp Array ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Genome Wide

scholarly journals Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility.

2021 ◽  
Author(s):  
Anna Kaitlyn Victor ◽  
Martin Donaldson ◽  
Daniel Johnson ◽  
Winston Miller ◽  
Lawrence Reiter
Keyword(s):  
Behavioral Problems ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Autism Spectrum ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Mitochondrial Defects ◽  
Mitochondrial Transcripts ◽  
Global Reduction

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk. Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings. Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD +ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons. Conclusions: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD +ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

scholarly journals Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility

2021 ◽  
Vol 14 ◽  
Author(s):  
A. Kaitlyn Victor ◽  
Martin Donaldson ◽  
Daniel Johnson ◽  
Winston Miller ◽  
Lawrence T. Reiter
Keyword(s):  
Behavioral Problems ◽  
Neurodevelopmental Disorder ◽  
Uniparental Disomy ◽  
Autism Spectrum ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Maternal Uniparental Disomy ◽  
Mitochondrial Defects ◽  
Mitochondrial Transcripts ◽  
Global Reduction

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk.Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings.Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons.Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.

Assessing the Clinical Utility of SNP Microarray for Prader-Willi Syndrome due to Uniparental Disomy

2017 ◽  
Vol 152 (2) ◽  
pp. 105-109 ◽  
Author(s):  
Stephanie L. Santoro ◽  
Sayaka Hashimoto ◽  
Aimee McKinney ◽  
Theresa Mihalic Mosher ◽  
Robert Pyatt ◽  
...  
Keyword(s):  
Single Case ◽  
Uniparental Disomy ◽  
Diagnostic Algorithm ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Multisystem Disorder ◽  
Maternal Uniparental Disomy ◽  
Snp Microarray ◽  
Imprinting Disorder ◽  
Regions Of Homozygosity

Maternal uniparental disomy (UPD) 15 is one of the molecular causes of Prader-Willi syndrome (PWS), a multisystem disorder which presents with neonatal hypotonia and feeding difficulty. Current diagnostic algorithms differ regarding the use of SNP microarray to detect PWS. We retrospectively examined the frequency with which SNP microarray could identify regions of homozygosity (ROH) in patients with PWS. We determined that 7/12 (58%) patients with previously confirmed PWS by methylation analysis and microsatellite-positive UPD studies had ROH (>10 Mb) by SNP microarray. Additional assessment of 5,000 clinical microarrays, performed from 2013 to present, determined that only a single case of ROH for chromosome 15 was not caused by an imprinting disorder or identity by descent. We observed that ROH for chromosome 15 is rarely incidental and strongly associated with hypotonic infants having features of PWS. Although UPD microsatellite studies remain essential to definitively establish the presence of UPD, SNP microarray has important utility in the timely diagnostic algorithm for PWS.

Mosaic trisomy 15 and prenatal genetic counselling: a case of Prader-Willi syndrome due to maternal uniparental disomy

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Mar Velilla Aparicio ◽  
Veronica Seidel ◽  
Maria Asunción Orera Clemente ◽  
Sylvia Marina Caballero ◽  
Manuel Sánchez Luna
Keyword(s):  
Growth Retardation ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Case Presentation ◽  
Maternal Uniparental Disomy ◽  
Low Level ◽  
Fetal Malformations ◽  
Level 2 ◽  
Mosaic Trisomy

Abstract Background Chromosome abnormalities are a frequent finding in prenatal invasive testing for fetal malformations and/or growth retardation. Case presentation We present a case of low level (8%) mosaic trisomy 15 detected on amniocentesis after fetal heart anomalies and IUGR (intrauterine growth retardation) were found on routine scan. Postnatal karyotype confirmed a very low level (2%) mosaicism in the skin but not in blood lymphocytes or in the urine. Methylation specific testing of chromosome 15 showed maternal uniparental disomy and consequently the newborn was diagnosed with Prader-Willi syndrome (PWS). Conclusions This case illustrates the need of further genetic testing in all trisomy 15 mosaicisms detected in prenatal invasive testing in order to screen for PWS, a more frequent entity than trisomy 15, altogether providing appropriate genetic counseling and adequate clinical management. The recommendation is applicable to prenatally detected mosaic trisomies of other chromosomes carrying imprinted genes, such as 7, 11 and 14.

Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy

The Lancet ◽  
2002 ◽  
Vol 359 (9301) ◽  
pp. 135-136 ◽  
Author(s):  
Harm Boer ◽  
Anthony Holland ◽  
Joyce Whittington ◽  
Jill Butler ◽  
Tessa Webb ◽  
...  
Keyword(s):  
Uniparental Disomy ◽  
Chromosome 15 ◽  
Prader Willi Syndrome ◽  
Psychotic Illness ◽  
Maternal Uniparental Disomy
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