Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene

Esposito, Teresa, Lea, Rod A., Maher, Bridget H., Moses, Dianne, Cox, Hannah C., Magliocca, Sara, Angius, Andrea, Nyholt, Dale R., Titus, Thomas, Kay, Troy, Gray, Nicholas A., Rastaldi, Maria P., Parnham, Alan, Gianfrancesco, Fernando and Griffiths, Lyn R. (2013) Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene. Human Molecular Genetics, 22 18: 3654-3666. doi:10.1093/hmg/ddt215


Author Esposito, Teresa
Lea, Rod A.
Maher, Bridget H.
Moses, Dianne
Cox, Hannah C.
Magliocca, Sara
Angius, Andrea
Nyholt, Dale R.
Titus, Thomas
Kay, Troy
Gray, Nicholas A.
Rastaldi, Maria P.
Parnham, Alan
Gianfrancesco, Fernando
Griffiths, Lyn R.
Title Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2013
Sub-type Article (original research)
DOI 10.1093/hmg/ddt215
Open Access Status
Volume 22
Issue 18
Start page 3654
End page 3666
Total pages 13
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2014
Language eng
Abstract Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13,which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
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Created: Thu, 29 Aug 2013, 08:39:47 EST by Dr Nicholas Gray on behalf of Sunshine Coast Clinical School