ENPP1 homozygous stop-loss variant causing generalized arterial calcifications of infancy: About a severe neonatal clinical case

Generalized Arterial Calcifications of Infancy (GACI) is an extremely rare autosomal recessive genetic condition, mostly due to pathogenic variations in the ENPP1 gene (GACI1, MIM #208000, ENPP1, MIM #173335). To date 46 likely pathogenic or pathogenic distinct variations in ENPP1 have been describe...

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Bibliographic Details
Published in:	European journal of medical genetics Vol. 66; no. 8; p. 104803
Main Authors:	Grosyeux, C., Jourdan, L., Jellimann, J.-M., Grandmougin, A., Bronner, M., Lambert, L., Bonnet, C.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Masson SAS 01-08-2023
Subjects:	ENPP1 Generalized arterial calcifications of infancy Neonatal arterial hypertension Pathologic calcification Stop-loss variant ENPP1 Stop-loss variant Generalized arterial calcifications of infancy Pathologic calcification Neonatal arterial hypertension
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Summary:	Generalized Arterial Calcifications of Infancy (GACI) is an extremely rare autosomal recessive genetic condition, mostly due to pathogenic variations in the ENPP1 gene (GACI1, MIM #208000, ENPP1, MIM #173335). To date 46 likely pathogenic or pathogenic distinct variations in ENPP1 have been described, including nonsense, frameshift, missense, splicing variations, and large deletions. Here we report a case of GACI in a male newborn with a homozygous stop-loss variant in ENPP1 treated in Nancy Regional University Maternity Hospital. Based on proband main clinical signs, clinical exome sequencing was performed and showed a deletion of one nucleotide leading to frameshift and stop-loss (NM_006208.3 (ENPP1):c.2746del,p.(Thr916Hisfs*23)). Clinical presentation is characterized by primary neonatal arterial hypertension resulting in hypertrophic cardiomyopathy decompensated by three cardiogenic shocks and a neonatal deep right sylvian stroke. The child died at 24 days of life. This is the first report of a pathogenic stop-loss variant in ENPP1. It is an opportunity to remind clinicians of GACI disease, a rare and severe etiology in neonates with severe hypertension, and possibility of bisphosphonates therapy.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1769-7212 1878-0849
DOI:	10.1016/j.ejmg.2023.104803