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

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.