Shwachman–Diamond syndrome due to biallelic EFL1 variants with complex and fatal clinical course in early infancy

Abstract

Summary: Shwachman–Diamond syndrome represents a clinically and genetically heterogeneous disorder. We report on an infant with a very severe, fatal clinical course caused by biallelic EFL1 variants: c.89A>G, p.(His30Arg), and c.2599A>G, p.(Asn867Asp). Functional analysis of patient‐derived B‐lymphoblastoid and SV40‐transformed fibroblast cell lines suggests that the compound heterozygous EFL1 variants impaired mature ribosome formation leading to compromised protein synthesis, ultimately resulting in a severe form of Shwachman–Diamond syndrome.