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

American Journal of Medical Genetics. Part a
François LecoquierreGaël Nicolas

Abstract

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. We performed exome sequencing in a patient exhibiting a syndromic developmental delay and in her unaffected parents and report the phenotypic features. 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. 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.

References

Sep 8, 2010·Nucleic Acids Research·Israel S FernándezOscar Llorca
Oct 19, 2014·JAMA : the Journal of the American Medical Association·Hane LeeStanley F Nelson
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Apr 23, 2019·Brain : a Journal of Neurology·Lou GrangeonGaël Nicolas

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Citations

Feb 21, 2021·American Journal of Medical Genetics. Part a·Norah AltuwaijriFowzan S Alkuraya
Nov 12, 2021·American Journal of Medical Genetics. Part a·Ghada M H Abdel-SalamJames R Lupski

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