Confirmation and further delineation of the SMG9‐deficiency syndrome, a rare and severe developmental disorder

• Published in: American journal of medical genetics. Part A Vol. 179; no. 11; pp. 2257 - 2262
• Main Authors: Lecoquierre, François, Bonnevalle, Antoine, Chadie, Alexandra, Gayet, Claire, Dumant‐Forest, Clémentine, Renaux‐Petel, Mariette, Leca, Jean‐Baptiste, Hazelzet, Tristan, Brasseur‐Daudruy, Marie, Louillet, Ferielle, Muraine, Marc, Coutant, Sophie, Quenez, Olivier, Boland, Anne, Deleuze, Jean‐François, Frebourg, Thierry, Goldenberg, Alice, Saugier‐Veber, Pascale, Guerrot, Anne‐Marie, Nicolas, Gaël
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2019; Wiley Subscription Services, Inc; Wiley
• Subjects: Cleft lip/palate; Developmental disabilities; Genetics; Growth rate; heart and brain malformation; Life Sciences; nonsense mediated decay; SMG9; heart and brain malformation; SMG9; nonsense mediated decay
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.61317

Introduction SMG9 deficiency is an extremely rare autosomal recessive condition originally described in three patients from two families harboring homozygous truncating SMG9 variants in a context of severe syndromic developmental disorder. To our knowledge, no additional patient has been described since this first report. Methods We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. Results Our patient presented with a syndromic association of severe global developmental delay and diverse malformations, including cleft lip and palate, facial dysmorphic features, brain abnormalities, heart defect, growth retardation, and severe infections. She carried a novel SMG9 homozygous variant NM_019108.3:c.1177C>T, p.(Gln393*), while her unaffected parents were both heterozygous. Conclusions We confirm that bi‐allelic truncating SMG9 variants cause a severe developmental syndrome including brain and heart malformations associated with facial dysmorphic features, severe growth and developmental delay with or without ophthalmological abnormalities, severe feeding difficulties, and life‐threatening infections.