2. Academic Validation
  3. Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome

Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome

  • J Med Genet. 2017 Jun;54(6):399-403. doi: 10.1136/jmedgenet-2016-104237.
Rasim Ozgur Rosti 1,  Bethany N Sotak 1,  Stephanie L Bielas 2,  Gifty Bhat 3 4,  Jennifer L Silhavy 1,  Ayca Dilruba Aslanger 5,  Umut Altunoglu 6,  Ilmay Bilge 7,  Mehmet Tasdemir 7,  Amanda D Yzaguirrem 1,  Damir Musaev 1,  Sofia Infante 1,  Whitney Thuong 1,  Isaac Marin-Valencia 3,  Stanley F Nelson 8,  Hulya Kayserili 5 9,  Joseph G Gleeson 1 3
Affiliations

Affiliations

  • 1 Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
  • 2 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
  • 3 Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, New York, USA.
  • 4 Division of Pediatric Genetics
, The Children's Hospital at Montefiore, Bronx, Bronx, New York, USA.
  • 5 Department of Medical Genetics, Koç University Hospital, Istanbul 34010, Turkey.
  • 6 Department Medical Genetics, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
  • 7 Department of Pediatric Nephrology, Koç University Hospital, Istanbul, Turkey.
  • 8 Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
  • 9 Department of Medical Genetics, Koç University, School of Medicine (KUSoM), Istanbul, Turkey.
PMID: 28280135 DOI: 10.1136/jmedgenet-2016-104237
Abstract

Background: Microcephaly with nephrotic syndrome is a rare co-occurrence, constituting the Galloway-Mowat syndrome (GAMOS), caused by mutations in WDR73 (OMIM: 616144). However, not all patients harbour demonstrable WDR73 deleterious variants, suggesting that there are Other yet unidentified factors contributing to GAMOS aetiology.

Methods: Autozygosity mapping and candidate analysis was used to identify deleterious variants in consanguineous families. Analysis of patient fibroblasts was used to study splicing and alterations in cellular function.

Results: In two consanguineous families with five affected individuals from Turkey with a GAMOS-like presentation, we identified a shared homozygous variant leading to partial exon 4 skipping in nucleoporin, 107-KD (NUP107). The founder mutation was associated with concomitant reduction in NUP107 protein and in the obligate binding partner NUP133 protein, as well as density of nuclear pores in patient cells.

Conclusion: Recently, NUP107 was suggested as a candidate in a family with nephrotic syndrome and developmental delay. Other NUP107-reported cases had isolated renal phenotypes. With the addition of these individuals, we implicate an allele-specific critical role for NUP107 in the regulation of brain growth and a GAMOS-like presentation.

Keywords

FSGS; Galloway-Mowat syndrome; NUP107; microcephaly; steroid-resistant nephrotic syndrome.

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