Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations
BackgroundFocal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.MethodsIn this report, we describe a sibling pair with NUP93 muta...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2022.915174/full |
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| author | Rachel K. Cason Anna Williams Megan Chryst-Stangl Guanghong Wu Kinsie Huggins Kaye E. Brathwaite Brandon M. Lane Larry A. Greenbaum Vivette D. D’Agati Rasheed A. Gbadegesin |
| author_facet | Rachel K. Cason Anna Williams Megan Chryst-Stangl Guanghong Wu Kinsie Huggins Kaye E. Brathwaite Brandon M. Lane Larry A. Greenbaum Vivette D. D’Agati Rasheed A. Gbadegesin |
| author_sort | Rachel K. Cason |
| collection | DOAJ |
| description | BackgroundFocal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.MethodsIn this report, we describe a sibling pair with NUP93 mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in NUP93 as well as for APOL1 high-risk genotypes.ResultsWe identified segregating compound heterozygous NUP93 variants (1) c.1772G > T p.G591V, 2) c.2084T > C p.L695S) in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the APOL1 high-risk genotype.ConclusionTo the best of our knowledge, this is the first report of cFSGS in patients with NUP93 mutations, based on this report, mutations in NUP93 and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS. |
| first_indexed | 2024-04-13T21:23:35Z |
| format | Article |
| id | doaj.art-d4df45f8d9b84a06aefb21928dcd2d26 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-13T21:23:35Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-d4df45f8d9b84a06aefb21928dcd2d262022-12-22T02:29:24ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602022-07-011010.3389/fped.2022.915174915174Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene MutationsRachel K. Cason0Anna Williams1Megan Chryst-Stangl2Guanghong Wu3Kinsie Huggins4Kaye E. Brathwaite5Brandon M. Lane6Larry A. Greenbaum7Vivette D. D’Agati8Rasheed A. Gbadegesin9Division of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Pediatric Nephrology, Children’s Hospital at Montefiore, The Bronx, NY, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesDivision of Pediatric Nephrology, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, United StatesDepartment of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, United StatesDivision of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United StatesBackgroundFocal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.MethodsIn this report, we describe a sibling pair with NUP93 mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in NUP93 as well as for APOL1 high-risk genotypes.ResultsWe identified segregating compound heterozygous NUP93 variants (1) c.1772G > T p.G591V, 2) c.2084T > C p.L695S) in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the APOL1 high-risk genotype.ConclusionTo the best of our knowledge, this is the first report of cFSGS in patients with NUP93 mutations, based on this report, mutations in NUP93 and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS.https://www.frontiersin.org/articles/10.3389/fped.2022.915174/fullnephrotic syndromefocal segmental glomerulosclerosiscollapsing FSGSnucleoporin genesAPOL1 |
| spellingShingle | Rachel K. Cason Anna Williams Megan Chryst-Stangl Guanghong Wu Kinsie Huggins Kaye E. Brathwaite Brandon M. Lane Larry A. Greenbaum Vivette D. D’Agati Rasheed A. Gbadegesin Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations Frontiers in Pediatrics nephrotic syndrome focal segmental glomerulosclerosis collapsing FSGS nucleoporin genes APOL1 |
| title | Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations |
| title_full | Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations |
| title_fullStr | Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations |
| title_full_unstemmed | Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations |
| title_short | Collapsing Focal Segmental Glomerulosclerosis in Siblings With Compound Heterozygous Variants in NUP93 Expand the Spectrum of Kidney Phenotypes Associated With Nucleoporin Gene Mutations |
| title_sort | collapsing focal segmental glomerulosclerosis in siblings with compound heterozygous variants in nup93 expand the spectrum of kidney phenotypes associated with nucleoporin gene mutations |
| topic | nephrotic syndrome focal segmental glomerulosclerosis collapsing FSGS nucleoporin genes APOL1 |
| url | https://www.frontiersin.org/articles/10.3389/fped.2022.915174/full |
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