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. 2025 Oct 15;13(10):e71230.
doi: 10.1002/ccr3.71230. eCollection 2025 Oct.

A Prenatal Diagnosis of Verheij Syndrome in a Fetus Harboring a de novo PUF60 Variant

Catia Mio  1 , Maria Orsaria  2 , Alessandra Franzoni  3 , Elisa Bregant  3 , Elena Betto  3 , Jessica Zucco  3 , Eliana Demori  3 , Giuseppe Damante  1   3 , Flavio Faletra  1   3
Affiliations

A Prenatal Diagnosis of Verheij Syndrome in a Fetus Harboring a de novo PUF60 Variant

Catia Mio et al. Clin Case Rep. .

Abstract

This case illustrates how trio-based exome sequencing can uncover de novo Poly-U-binding splicing factor 60-KD (PUF60) gene variants responsible for Verheij syndrome (VRJS) in utero, even in the absence of classic features such as growth restriction. Our findings broaden the prenatal phenotype and underscore the role of advanced genomic tools in evaluating polymalformative syndromes.

Keywords: PUF60; Verheij syndrome; exome sequencing; polymalformative syndrome; prenatal diagnosis; spliceosomopathy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Major craniofacial abnormalities detected in our proband. Body view (left) and face (right). Despite the early gestational age, the fetus presented some of the typical features of VRJS such as skull anomalies (turricephaly, arrowed—a), hypertelorism, short nose with anteverted nares, long nasolabial filter (arrowed—b), and low‐set malformed ears (arrowed—c).
FIGURE 2
FIGURE 2
Major visceral abnormalities detected in our proband. (A) Straightened right aortic arch (arrowed). (B) Gallbladder and extrahepatic biliary tract hypoplasia (arrowed). (C) ureters and urinary bladder ectasia, bilateral kidney hypoplasia (arrowed). (D) abnormality of intestinal rotation and mesenteric attachment of the sigmoid colon (arrowed).
See this image and copyright information in PMC

References

    1. Verheij J. B. G. M., de Munnik S. A., Dijkhuizen T., et al., “An 8.35 Mb Overlapping Interstitial Deletion of 8q24 in Two Patients With Coloboma, Congenital Heart Defect, Limb Abnormalities, Psychomotor Retardation and Convulsions,” European Journal of Medical Genetics 52, no. 5 (2009): 353–357, 10.1016/j.ejmg.2009.05.006. - DOI - PubMed
    1. Dauber A., Golzio C., Guenot C., et al., “SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy‐Number Variant,” American Journal of Human Genetics 93, no. 5 (2013): 798–811, 10.1016/j.ajhg.2013.09.010. - DOI - PMC - PubMed
    1. Low K. J., Ansari M., Jamra R. A., et al., “PUF60 Variants Cause a Syndrome of ID, Short Stature, Microcephaly, Coloboma, Craniofacial, Cardiac, Renal and Spinal Features,” European Journal of Human Genetics 25, no. 5 (2017): 552–559, 10.1038/ejhg.2017.27. - DOI - PMC - PubMed
    1. Hoogenboom A., Falix F. A., van der Laan L., et al., “Novel PUF60 Variant Suggesting an Interaction Between Verheij and Cornelia de Lange Syndrome: Phenotype Description and Review of the Literature,” European Journal of Human Genetics 32, no. 4 (2024): 435–439, 10.1038/s41431-023-01527-1. - DOI - PMC - PubMed
    1. Hastings M. L., Allemand E., Duelli D. M., Myers M. P., and Krainer A. R., “Control of Pre‐mRNA Splicing by the General Splicing Factors PUF60 and U2AF65,” PLoS One 2, no. 6 (2007): e538, 10.1371/journal.pone.0000538. - DOI - PMC - PubMed

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