A Biallelic Variant in FRA10AC1 Is Associated With Neurodevelopmental Disorder and Growth Retardation

Norah Alsaleh; Amal Alhashem; Brahim Tabarki; Sarar Mohamed; Essa Alharby; Fowzan S Alkuraya; Naif A M Almontashiri

doi:10.1212/NXG.0000000000200010

A Biallelic Variant in FRA10AC1 Is Associated With Neurodevelopmental Disorder and Growth Retardation

Neurol Genet. 2022 Jul 7;8(4):e200010. doi: 10.1212/NXG.0000000000200010. eCollection 2022 Aug.

Authors

Norah Alsaleh¹, Amal Alhashem¹, Brahim Tabarki¹, Sarar Mohamed¹, Essa Alharby¹, Fowzan S Alkuraya¹, Naif A M Almontashiri¹

Affiliation

¹ Division of Medical Genetics and Metabolic Medicine (N.A., S.M.), Department of Pediatrics, Prince Sultan Military Medical City; Department of Anatomy and Cell Biology (A.A.), College of Medicine, Alfaisal University; Division of Neurology (A.A., B.T.), Department of Pediatrics, Prince Sultan Military Medical City; Department of Pediatrics (S.M.), College of Medicine, Alfaisal University, Riyadh; Center for Genetics and Inherited Diseases (E.A., N.A.M.A.), Taibah University, Almadinah Almunwarah; Department of Translational Genomics (F.S.A.), Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh; Faculty of Applied Medical Sciences (N.A.M.A.), Taibah University, Almadinah Almunwarah; and Noor Diagnostics and Discovery (N.A.M.A.), Innovation Cluster, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.

Abstract

Objectives: Our objective was to identify the genetic cause in a family with a remarkable history of neurodevelopmental disease and growth retardation.

Methods: A neurologic evaluation was performed, and DNA samples were obtained from the affected siblings and parents to perform whole-exome sequencing (WES).

Results: Both siblings presented with dysmorphic features, failure to thrive, global developmental delay, generalized hypotonia, feeding problems, and congenital heart disease. WES revealed a homozygous nonsense variant in the FRA10AC1 gene in both siblings.

Discussion: A recent study has reported the first association of biallelic variants in the spliceosomal C complex gene, FRA10AC1, with syndromic neurodevelopmental disease and growth retardation in 5 patients from 3 consanguineous families complex. In this study, we provide the first confirmation of the reported FRA10AC1-related neurologic syndrome in an additional family.