{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:29:45Z","timestamp":1777555785175,"version":"3.51.4"},"reference-count":19,"publisher":"BMJ","issue":"8","funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU 1240\/17-1"],"award-info":[{"award-number":["KU 1240\/17-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,4,28]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:p>Biallelic variants in <jats:italic>NUP107<\/jats:italic> cause isolated or syndromic steroid-resistant nephrotic syndrome (SRNS), characterised by proteinuria, hypoalbuminaemia and focal segmental glomerulosclerosis that progresses to end-stage renal disease. Patients with syndromic SRNS have microcephaly, developmental delay or intellectual disability and short stature. Simplified gyration is observed in some individuals. We report on a 2-year-old girl with novel biallelic <jats:italic>NUP107<\/jats:italic> variants, c.2606G&gt;T; p.(Gly869Val) and c.1576+1G&gt;A, proteinuria and a severe neurodevelopmental disorder with microcephaly, developmental delay, early-onset seizures, sensorineural hearing loss and brain structural anomalies, including simplified gyral pattern and hypoplasia of the corpus callosum, pons, brainstem and cerebellum. NUP107 is part of the NUP107-160 complex, which, together with other proteins termed nucleoporins, forms the nuclear pore complex (NPC). The NPC regulates nucleocytoplasmic transport and other cellular processes. In patient-derived fibroblasts, we identified aberrantly spliced <jats:italic>NUP107<\/jats:italic> mRNAs with a frameshift and premature stop codon leading to non-sense-mediated mRNA decay, reduced levels of <jats:italic>NUP107<\/jats:italic> transcripts, reduced NUP107 and NUP133 proteins, and a reduced NPC number. In addition, an abnormal nucleolar morphology was found in patient-derived cells. Our functional data support the conclusion that the <jats:italic>NUP107<\/jats:italic> variants underlie the patient\u2019s phenotype, thereby broadening the clinical spectrum associated with <jats:italic>NUP107<\/jats:italic> variants to include abnormal brain development.<\/jats:p>","DOI":"10.1136\/jmg-2025-110671","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T13:20:21Z","timestamp":1746969621000},"page":"497-501","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Novel biallelic <i>NUP107<\/i> variants affect the nuclear pore complex and expand the clinical spectrum to include brain malformations"],"prefix":"10.1136","volume":"62","author":[{"given":"Loisa Dana","family":"Bonde","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Hecher","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"},{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malik","family":"Alawi","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten P","family":"Forbes","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Queen Elizabeth University Hospital, Glasgow, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph 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