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Purpose: To determine whether a history of conception by assisted reproductive technology (ART) is associated with occurrence of one or more imprinting disorders of either maternal or paternal origin.
Methods: We implemented a systematic review of scholarly literature followed by comprehensive meta-analysis to quantitatively synthesize data from reports relating to use of ART to occurrence of any imprinting disorder of humans, including Beckwith-Wiedemann (BWS), Angelman (AS), Prader-Willi (PWS), and Silver-Russell (SRS) syndromes, as well as transient neonatal diabetes mellitus (TNDB) and sporadic retinoblasoma (RB).
Results: The systematic review identified 13 reports presenting unique data from 23 studies that related conception following ART to occurrence of imprinting disorders. Multiple studies of four disorder were identified, for which meta-analysis yielded the following summary estimates of associations with a history of ART: AS, summary odds ratio (sOR) = 4.7 (95% confidence interval (CI) 2.6-8.5, 4 studies); BWS, sOR = 5.8 (95% CI 3.1-11.1, 8 studies); PWS, sOR = 2.2 (95% CI 1.6-3.0, 6 studies); SRS, sOR = 11.3 (95% CI 4.5-28.5, 3 studies). Only one study reported on each of TNDB and RB.
Conclusion: Published data reveal positive associations between history of ART conception and each of four imprinting disorders. Reasons for these associations warrant further investigation.
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http://dx.doi.org/10.1007/s10815-018-1173-x | DOI Listing |
Case Rep Genet
August 2025
Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.
Uniparental disomy (UPD), the inheritance of two copies of a chromosome from one parent, can lead to recessive genetic disorders or imprinting effects. We report a case of autosomal recessive glycogen storage disease type 4 (GSD IV) due to maternal UPD of chromosome 3, representing the first reported instance of UPD leading to this rare disorder. To avoid an unjustified claim of misattributed paternity, the possibility of UPD should always be kept in mind in cases with the unique finding of the homozygous pathogenic variant only present in one parent.
View Article and Find Full Text PDFAnn Hum Biol
December 2025
Growth and Development Department, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.
Background: Prader-Willi syndrome (PWS) is a complex genetic disorder characterised by infantile hypotonia, early-onset obesity, intellectual disability, hypopigmentation, small hands and feet, short stature, hypogonadism, and distinctive facial features.
Aim: To generate and report growth curves for height, sitting height, hands and feet length for Argentine children with Prader-Willi syndrome (PWS) without growth hormone treatment.
Subjects And Methods: A total of 1174 anthropometric measures were obtained from 167 children (82 boys) aged 0-19 years attending Hospital Garrahan between 1992 and 2019.
Commun Biol
September 2025
UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of maternally-inherited UBE3A. In neurons, paternally-inherited UBE3A is silenced in cis by a long non-coding RNA called Ube3a-ATS. Here, we found that Neisseria meningitidis Cas9 with two mutations (D15A and H587A) in the nuclease domains (dNmCas9) can unsilence the dormant paternal Ube3a allele in mouse and human neurons when targeted to Snord115 snoRNA genes located in introns of Ube3a-ATS.
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Roche Pharma Research and Early Development, Neuroscience and Rare Disease discovery and translational area, Roche Innovation Center Basel, Basel 4070, Switzerland.
Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of neuronal ubiquitin E3 ligase UBE3A, with no available treatment. Restoring UBE3A by downregulating the paternally cis-acting long noncoding antisense transcript (UBE3A-ATS) is a potentially disease modifying strategy. However, developing molecules targeting human UBE3A-ATS is challenging due to its selective expression in mature neurons and lack of sequence conservation across species.
View Article and Find Full Text PDFMol Autism
August 2025
Dept. of Clinical Genetics, Erasmus MC Center of Expertise for Neurodevelopmental Disorders (ENCORE), Erasmus MC, Rotterdam, The Netherlands.
Background: Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene.
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