Justin O Szot, Hartmut Cuny, Ella Mma Martin, Delicia Z Sheng, Kavitha Iyer, Stephanie Portelli, Vivien Nguyen, Jessica M Gereis, Dimuthu Alankarage, David Chitayat, Karen Chong, Ingrid M Wentzensen, Catherine Vincent-Delormé, Alban Lermine, Emma Burkitt-Wright, Weizhen Ji, Lauren Jeffries, Lynn S Pais, Tiong Y Tan, James Pitt, Cheryl A Wise, Helen Wright, Israel D Andrews, Brianna Pruniski, Theresa A Grebe, Nicole Corsten-Janssen, Katelijne Bouman, Cathryn Poulton, Supraja Prakash, Boris Keren, Natasha J Brown, Matthew F Hunter, Oliver Heath, Saquib A Lakhani, John H McDermott, David B Ascher, Gavin Chapman, Kayleigh Bozon, Sally L Dunwoodie
Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation...
February 15, 2024: Journal of Clinical Investigation