Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome.

J Am Soc Nephrol 2008 Feb 23;19(2):365-71. Epub 2008 Jan 23.

Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.

Mutations in the gene encoding podocin (NPHS2) cause autosomal recessive steroid-resistant nephrotic syndrome (SRNS). For addressing the possibility of a genotype-phenotype correlation between podocin mutations and age of onset, a worldwide cohort of 430 patients from 404 different families with SRNS were screened by direct sequencing. Recessive podocin mutations were present in 18.1% (73 of 404) of families with SRNS, and 69.9% of these mutations were nonsense, frameshift, or homozygous R138Q. Patients with these mutations manifested symptoms at a significantly earlier age (mean onset <1.75 years) than any other patient group, with or without podocin mutations, in this study (mean onset >4.17 yr). All but one patient affected by truncating or homozygous R138Q mutations developed SRNS before 6 yr of age. Patient groups with other recessive podocin mutations, with single heterozygous podocin mutations, with sequence variants, and with no podocin changes could not be distinguished from each other on the basis of age of onset. In conclusion, nephrotic syndrome in children with truncating or homozygous R138Q mutations manifests predominantly before 6 yr of life, and the onset of disease is significantly earlier than for any other podocin mutations. Because the age of onset can vary by several years among those with identical mutations, additional factors may modify the phenotype.

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2007040452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2396749PMC
February 2008
2 Reads

Publication Analysis

Top Keywords

podocin mutations
24
age onset
20
homozygous r138q
12
mutations
12
nephrotic syndrome
12
steroid-resistant nephrotic
8
r138q mutations
8
mutations age
8
truncating homozygous
8
404 families
8
families srns
8
recessive podocin
8
podocin
7
onset
6
age
6
mutations developed
4
srns 699%
4
patient truncating
4
developed srns
4
181% 404
4

References

(Supplied by CrossRef)

Mol Cell 1998

Similar Publications