|
|
| PMID |
|
|
| TITLE |
|
| Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene. |
|
| 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. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| aheadofprint |
2013/05/16 |
| aheadofprint |
2013/06/03 |
| entrez |
2013/05/21 06:00 |
| pubmed |
2013/05/21 06:00 |
| medline |
2014/03/19 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Esposito T |
|
Esposito |
Teresa |
T |
|
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, National Research Council of Italy, Naples, Italy. |
| Lea RA |
|
Lea |
Rod A |
RA |
|
|
| Maher BH |
|
Maher |
Bridget H |
BH |
|
|
| Moses D |
|
Moses |
Dianne |
D |
|
|
| Cox HC |
|
Cox |
Hannah C |
HC |
|
|
| Magliocca S |
|
Magliocca |
Sara |
S |
|
|
| Angius A |
|
Angius |
Andrea |
A |
|
|
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
|
|
| Titus T |
|
Titus |
Thomas |
T |
|
|
| Kay T |
|
Kay |
Troy |
T |
|
|
| Gray NA |
|
Gray |
Nicholas A |
NA |
|
|
| Rastaldi MP |
|
Rastaldi |
Maria P |
MP |
|
|
| Parnham A |
|
Parnham |
Alan |
A |
|
|
| Gianfrancesco F |
|
Gianfrancesco |
Fernando |
F |
|
|
| Griffiths LR |
|
Griffiths |
Lyn R |
LR |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 22 |
| ISSUE: 18 |
| TITLE: Human molecular genetics |
| ISOABBREVIATION: Hum. Mol. Genet. |
| YEAR: 2013 |
| MONTH: Sep |
| DAY: 15 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2083 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Hum Mol Genet |
| COUNTRY: England |
| ISSNLINKING: 0964-6906 |
| NLMUNIQUEID: 9208958 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Animals |
|
| Australia |
|
| Child |
|
| Child, Preschool |
|
| Exome |
|
| Female |
|
| Genes, X-Linked |
|
| Genetic Diseases, X-Linked |
genetics |
| Genetic Linkage |
genetics |
| Glomerulosclerosis, Focal Segmental |
genetics |
| HEK293 Cells |
genetics |
| Heart Block |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Mice |
genetics |
| Middle Aged |
genetics |
| Mutation |
genetics |
| N-Acetylglucosaminyltransferases |
genetics |
| Nucleocytoplasmic Transport Proteins |
genetics |
| Organ Specificity |
genetics |
| Pedigree |
genetics |
| RNA-Binding Proteins |
genetics |
| Sequence Analysis, DNA |
genetics |
| Young Adult |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
NXF5 protein, human |
| 0 |
Nucleocytoplasmic Transport Proteins |
| 0 |
RNA-Binding Proteins |
| EC 2.4.1.- |
ALG13 protein, human |
| EC 2.4.1.- |
N-Acetylglucosaminyltransferases |
|
| OTHER ID's |
|
|
|
