title: Homozygous mutation inNUP107leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome.
abstract: Microcephaly with nephrotic syndrome is a rare co-occurrence, constituting the Galloway-Mowat syndrome (GAMOS), caused by mutations inWDR73(OMIM: 616144). However, not all patients harbour demonstrableWDR73deleterious variants, suggesting that there are other yet unidentified factors contributing to GAMOS aetiology.
  
  
  
  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.
  
  
  
  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 innucleoporin, 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.
  
  
  
  Recently,NUP107was suggested as a candidate in a family with nephrotic syndrome and developmental delay. OtherNUP107-reported cases had isolated renal phenotypes. With the addition of these individuals, we implicate an allele-specific critical role forNUP107in the regulation of brain growth and a GAMOS-like presentation.
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Rasim Ozgur
authors.initials: RO
authors.lastname: Rosti
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Sotak
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Bielas
authors.affiliation: Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, New York, USA.|Division of Pediatric Genetics , The Children's Hospital at Montefiore, Bronx, Bronx, New York, USA.
authors.forename: Gifty
authors.initials: G
authors.lastname: Bhat
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Silhavy
authors.affiliation: Department of Medical Genetics, Koç University Hospital, Istanbul 34010, Turkey.
authors.forename: Ayca Dilruba
authors.initials: AD
authors.lastname: Aslanger
authors.affiliation: Department Medical Genetics, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
authors.forename: Umut
authors.initials: U
authors.lastname: Altunoglu
authors.affiliation: Department of Pediatric Nephrology, Koç University Hospital, Istanbul, Turkey.
authors.forename: Ilmay
authors.initials: I
authors.lastname: Bilge
authors.affiliation: Department of Pediatric Nephrology, Koç University Hospital, Istanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tasdemir
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Yzaguirrem
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Damir
authors.initials: D
authors.lastname: Musaev
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Infante
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Whitney
authors.initials: W
authors.lastname: Thuong
authors.affiliation: Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, New York, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Marin-Valencia
authors.affiliation: Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Nelson
authors.affiliation: Department of Medical Genetics, Koç University Hospital, Istanbul 34010, Turkey.|Department of Medical Genetics, Koç University, School of Medicine (KUSoM), Istanbul, Turkey.
authors.forename: Hulya
authors.initials: H
authors.lastname: Kayserili
authors.affiliation: Laboratory for Pediatric Brain Disease, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.|Laboratory for Pediatric Brain Disease, The Rockefeller University, New York, New York, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
mesh_terms: D000293:Adolescent; D002648:Child; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006551:Hernia, Hiatal / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007668:Kidney / Q000378:metabolism; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009401:Nephrosis / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000235:genetics*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D013256:Steroids / Q000378:metabolism*; D014421:Turkey
chemical_list: C512772:NUP107 protein, human; D028861:Nuclear Pore Complex Proteins; D011506:Proteins; D013256:Steroids; C000595586:WDR73 protein, human
keywords: FSGS; Galloway-Mowat syndrome; NUP107; microcephaly; steroid-resistant nephrotic syndrome