Clinical heterogeneity of NADSYN1-associated VCRL syndrome.
NAD deficiency disorder
NADSYN1
VCRL
spondylocostal dysostosis
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
06
03
2023
received:
26
01
2023
accepted:
12
03
2023
medline:
5
6
2023
pubmed:
24
3
2023
entrez:
23
3
2023
Statut:
ppublish
Résumé
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.
Substances chimiques
Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor
EC 6.3.5.-
NAD
0U46U6E8UK
NADSYN1 protein, human
EC 6.3.5.-
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114-120Informations de copyright
© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
Références
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