Corrigendum to: Heterozygous missense variant in EIF6 gene: A novel form of Shwachman–Diamond syndrome? (American Journal of Medical Genetics Part A, (2020), 182, 9, (2010-2020), 10.1002/ajmg.a.61758)

Thank you for publishing our manuscript entitled “Heterozygous Missense Variant in EIF6 gene: a novel form of Shwachman-Diamond Syndrome?” in the American Journal of Medical Genetics Part A (Volume 182, Issue 9, Pages 2010–2020).1 In this manuscript, we had reported a novel heterozygous de novo missense variant (c.182G>T (NM_002212.4), p.Arg61Leu) in the Eukaryotic Initiation Factor (EIF6) gene which was identified by exome sequencing (WES) of DNA from blood leukocytes of a 6-year-old Chinese boy with Shwachman-Diamond syndrome-like phenotype with transient bone marrow failure and persistent pancreatic insufficiency. After this publication, functional analyses were undertaken with collaborators to better understand the pathogenesis of this private EIF6 variant (c.182G>T, p.Arg61Leu) on Shwachman-Diamond syndrome (SDS). To our surprise, our analysis revealed that this EIF6 variant could rescue, rather than cause, the fitness defect associated with deficiency of the SBDS homolog in yeast. This unexpected and rather contradictory finding, prompted to us conduct some verifications. Sanger sequencing of gDNA from the proband's fibroblast failed to validate this EIF6 variant, suggesting that this SNP is a somatic variant present in leukocyte-derived gDNA, but not in the whole-body as would be germline variant. The targeted Sanger sequencing of SBDS, whose protein levels were reduced, identified likely pathogenic biallelic variants (c.183_184delTAinsCT; p.Lys62Ter and c.258+2T>C). This result was consistent with a clinical diagnosis of SDS. Complementation experiments performed in yeast suggest the somatically acquired EIF6 variant in this child, helps to rescue the germline ribosome defect due to biallelic mutations in SBDS. In view of these new findings, we would like to publish this corrigendum to our original manuscript. We would like to suggest that this EIF6 variant has been somatically acquired to rescue the germline ribosome defect due to biallelic mutations in SBDS. Part of this data have been reported in a recent publication in Nature Communications.2.