Case report: Compound heterozygous NUP85 variants cause autosomal recessive primary microcephaly

• DOI: 10.3389/fneur.2023.1124886
• Publication Date: 2023-02-09T07:25:19Z
• Authors: Ethiraj Ravindran; Gaetan Lesca; Louis Januel; Linus Goldgruber; Achim Dickmanns; Henri Margot; Angela M. Kaindl
• Keywords: Microcephaly; Nucleoporin; Compound heterozygosity; Loss function; Nuclear pore

Nucleoporin (NUP) 85 is a member of the Y-complex nuclear pore complex (NPC) that key for nucleocytoplasmic transport function, regulation mitosis, transcription, and chromatin organization. Mutations in various nucleoporin genes have been linked to several human diseases. Among them, NUP85 was childhood-onset steroid-resistant nephrotic syndrome (SRNS) four affected individuals with intellectual disability but no microcephaly. Recently, we broaden phenotype spectrum NUP85-associated disease by reporting variants two unrelated primary autosomal recessive microcephaly (MCPH) Seckel (SCKS) disorders (MCPH-SCKS) without SRNS. In this study, report compound heterozygous an index patient only MCPH phenotype, neither nor SRNS reported. We showed identified missense cause reduced cell viability patient-derived fibroblasts. Structural simulation analysis double predicted alter structure its interactions neighboring NUPs. Our study thereby further expands phenotypic disorder emphasizes crucial role brain development function.