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Case Reports
. 2023 Jul;104(1):114-120.
doi: 10.1111/cge.14328. Epub 2023 Mar 23.

Clinical heterogeneity of NADSYN1-associated VCRL syndrome

Marion Aubert-Mucca  1   2 , Caroline Janel  3 , Valérie Porquet-Bordes  2 , Olivier Patat  1 , Renaud Touraine  4 , Thomas Edouard  2 , Caroline Michot  5 , Aude Tessier  5 , Valérie Cormier-Daire  5   6 , Tania Attie-Bitach  5 , Geneviève Baujat  5
Affiliations
Case Reports

Clinical heterogeneity of NADSYN1-associated VCRL syndrome

Marion Aubert-Mucca et al. Clin Genet. 2023 Jul.

Abstract

The NADSYN1 gene [MIM*608285] encodes the NAD synthetase 1 enzyme involved in the final step of NAD biosynthesis, crucial for cell metabolism and organ embryogenesis. Perturbating the role of NAD biosynthesis results in the association of vertebral, cardiac, renal, and limb anomalies (VCRL). This condition was initially characterized as severe with perinatal lethality or developmental delay and complex malformations in alive cases. Sixteen NADSYN1-associated patients have been published so far. This study illustrates the wide phenotypic variability in NADSYN1-associated NAD deficiency disorder. We report the clinical and molecular findings in three novel cases, two of them being siblings with the same homozygous variant and presenting with either a very severe prenatal lethal or a mild phenotypic form. In addition to an exhaustive literature, we validate the expansion of the spectrum of NAD deficiency disorder. Our findings indicate that NAD deficiency disorder should be suspected not only in the presence of the full spectrum of VCRL, but even a single of the aforementioned organs is affected. Decreased plasmatic levels of NAD should then strongly encourage the screening for any of the genes responsible for a NAD deficiency disorder.

Keywords: NAD deficiency disorder; NADSYN1; VCRL; spondylocostal dysostosis.

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REFERENCES

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