The diagnostic journey of a patient with prader–willi-like syndrome and a unique homozygous snurf-snrpn variant; bio-molecular analysis and review of the literature

Karlijn Pellikaan, Geeske M. van Woerden, Lotte Kleinendorst, Anna G.W. Rosenberg, Bernhard Horsthemke, Christian Grosser, Laura J.C.M. van Zutven, Elisabeth F.C. van Rossum, Aart J. van der Lely, James L. Resnick, Hennie T. Brüggenwirth, Mieke M. van Haelst, Laura C.G. de Graaff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
112 Downloads (Pure)

Abstract

Prader–Willi syndrome (PWS) is a rare genetic condition characterized by hypotonia, intellectual disability, and hypothalamic dysfunction, causing pituitary hormone deficiencies and hyperphagia, ultimately leading to obesity. PWS is most often caused by the loss of expression of a cluster of genes on chromosome 15q11.2-13. Patients with Prader–Willi-like syndrome (PWLS) display features of the PWS phenotype without a classical PWS genetic defect. We describe a 46-year-old patient with PWLS, including hypotonia, intellectual disability, hyperphagia, and pituitary hormone deficiencies. Routine genetic tests for PWS were normal, but a homozygous missense variant NM_003097.3(SNRPN):c.193C>T, p.(Arg65Trp) was identified. Single nucleotide polymorphism array showed several large regions of homozygosity, caused by high-grade consanguinity between the parents. Our functional analysis, the ‘Pipeline for Rapid in silico, in vivo, in vitro Screening of Mutations’ (PRiSM) screen, showed that overexpression of SNRPN-p.Arg65Trp had a dominant negative effect, strongly suggesting pathogenicity. However, it could not be confirmed that the variant was responsible for the phenotype of the patient. In conclusion, we present a unique homozygous missense variant in SNURF-SNRPN in a patient with PWLS. We describe the diagnostic trajectory of this patient and the possible contributors to her phenotype in light of the current literature on the genotype–phenotype relationship in PWS.

Original languageEnglish
Article number875
JournalGenes
Volume12
Issue number6
DOIs
Publication statusPublished - 7 Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Fingerprint

Dive into the research topics of 'The diagnostic journey of a patient with prader–willi-like syndrome and a unique homozygous snurf-snrpn variant; bio-molecular analysis and review of the literature'. Together they form a unique fingerprint.

Cite this