Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2025 Jun 5;16(6):689.
doi: 10.3390/genes16060689.

Mixed Segmental Uniparental Disomy of Chromosome 15q11-q1 Coexists with Homozygous Variant in GNB5 Gene in Child with Prader-Willi and Lodder-Merla Syndrome

Tomasz Marczyk  1 , Maria Libura  2 , Beata Wikiera  3 , Magdalena Góralska  4 , Agnieszka Pollak  5 , Marlena Telenga  3 , Rafał Płoski  5 , Robert Śmigiel  3
Affiliations
Case Reports

Mixed Segmental Uniparental Disomy of Chromosome 15q11-q1 Coexists with Homozygous Variant in GNB5 Gene in Child with Prader-Willi and Lodder-Merla Syndrome

Tomasz Marczyk et al. Genes (Basel). .

Abstract

Background: Uniparental disomy (UPD) refers to the condition in which both chromosomes (or part of chromosome) of a pair are inherited from the same parent. There are two types of UPD: uniparental isodisomy (both chromosomes inherited from one parent are identical copies) and uniparental heterodisomy (two different chromosomes are inherited from one parent). UPD presents two primary developmental risks: recessive trait inheritance or an imprinting disorder. These risks may coexist, leading to an ultra-rare comorbidity. Managing the comorbidities associated with rare diseases presents unique clinical challenges.

Results: The existence of such phenomena is evidenced by our case report of a boy who was ultimately diagnosed with two rare diseases: Prader-Willi syndrome (PWS), due to the maternal uniparental disomy of chromosome 15 (UPD), and autosomal recessive Lodder-Merla type 1 syndrome, linked to a novel pathogenic variant in the G protein subunit β 5 (GNB5) gene, as detailed in this paper.

Conclusions: An unusual or severe phenotype in a patient diagnosed with PWS should invariably prompt the consideration of a comorbid genetic disease attributable to genes located in the PWS critical region of chromosome 15q, or elsewhere on chromosome 15. In cases of epileptic encephalopathy with cardiac arrhythmia, prompt consultation with a cardiologist and comprehensive genetic testing are essential to reduce the risks associated with untreated arrhythmia and ensure the provision of appropriate and safe anti-epileptic therapy. The presented case provides further support for the hypothesis that uniparental disomy may serve as an underlying cause of Lodder-Merla syndrome. This underscores the significance of comprehensive genetic testing, encompassing parental testing and familial cascade testing (in selected cases where there is consanguinity, or the likelihood of close common ancestral background between partners) to establish the recurrence risk.

Keywords: GNB5; IDDCA; LADCI; Lodder–Merla syndrome; Prader–Willi syndrome; maternal uniparental disomy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors alone are responsible for the content and writing of this article. All authors have read and approved the final manuscript.

References

    1. Fermin Gutierrez M.A., Daley S.F., Mendez M.D. Prader-Willi Syndrome. [(accessed on 25 January 2025)]; Available online: https://www.ncbi.nlm.nih.gov/books/NBK553161/ - PubMed
    1. Butler M.G. Prader-Willi Syndrome and Chromosome 15q11.2 BP1-BP2 Region: A Review. Int. J. Mol. Sci. 2023;24:4271. doi: 10.3390/ijms24054271. - DOI - PMC - PubMed
    1. Engel E. A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements. Eur. J. Hum. Genet. 2006;14:1158–1169. doi: 10.1038/sj.ejhg.5201619. - DOI - PubMed
    1. Del Gaudio D., Shinawi M., Astbury C., Tayeh M.K., Deak K.L., Raca G., ACMG Laboratory Quality Assurance Committee Diagnostic testing for uniparental disomy: A points to consider statement from the American College of Medical Genetics and Genomics (ACMG) Genet. Med. 2020;22:1133–1141. doi: 10.1038/s41436-020-0782-9. - DOI - PubMed
    1. Erger F., Burau K., Elsser M., Zimmermann K., Moog U., Netzer C. Uniparental isodisomy as a cause of recessive Mendelian disease: A diagnostic pitfall with a quick and easy solution in medium/large NGS analyses. Eur. J. Hum. Genet. 2018;26:1392–1395. doi: 10.1038/s41431-018-0195-2. - DOI - PMC - PubMed

Publication types

Substances

LinkOut - more resources