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Shwachman-Diamond syndrome (SDS) is a rare multisystem ribosomopathy typically inherited in an autosomal recessive manner, most often due to biallelic SBDS mutations. A single de novo heterozygous missense variant in EIF6 (c.182G>T (p.Arg61Leu)) was identified in a 6-year-old Chinese boy presenting with pancytopenia, hepatosplenomegaly, developmental delay, exocrine pancreatic insufficiency with malabsorption, and growth delay (PMID:32657013). EIF6 functions in 60S ribosomal subunit maturation and is released by SBDS and EFL1 proteins; structural analyses predict the p.Arg61Leu change may perturb ribosome biogenesis consistent with SDS pathogenesis. No additional unrelated probands or familial segregation data have been reported, and no in vivo functional validation is available. Consequently, the genetic and experimental support for EIF6 as an SDS‐causing gene remains limited. Identification of further independent cases and direct functional assays are required to confirm EIF6 as a novel dominant locus for SDS-like phenotypes.
Gene–Disease AssociationLimitedSingle de novo proband with SDS-like phenotype and no replication Genetic EvidenceLimitedSingle proband, no familial segregation Functional EvidenceLimitedInferred from structural modeling, no direct functional assays |