Open AccessRecessive NPHS2 (Podocin) Mutations Are Rare in Adult-Onset Idiopathic Focal Segmental Glomerulosclerosis
Author(s) -
Ning He,
Alireza Zahirieh,
YanAi Mei,
Brian Lee,
Sean Senthilnathan,
Betty Wong,
Bettina Mucha,
Friedhelm Hildebrandt,
David E. C. Cole,
Daniel C. Cattran,
York Pei
Publication year - 2007
Publication title -
clinical journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.755
H-Index - 151
eISSN - 1555-905X
pISSN - 1555-9041
DOI - 10.2215/cjn.02690806
Subject(s) - podocin , medicine , focal segmental glomerulosclerosis , minimal change disease , compound heterozygosity , missense mutation , population , mutation , pathology , genetics , glomerulonephritis , biology , gene , proteinuria , podocyte , kidney , environmental health
Recessive NPHS2 (podocin) mutations account for up to approximately 30% of steroid-resistant idiopathic FSGS in children and are associated with a reduced risk for disease recurrence after renal transplantation. R229Q, a missense variant that is present in 3.6% of the white population, has been implicated as a common disease-causing mutation. Given these clinical implications, we examined the role of NPHS2 mutations in a cohort of patients with adult-onset FSGS. We used denaturing HPLC to screen for heterozygous and homozygous gene variants in PCR-amplified DNA fragments that contained all exons and splice junctions of NPHS2. Bidirectional sequencing was performed to define all of the gene variants detected. With the use of the denaturing HPLC in a single-blind pilot study, 40 of 43 known NPHS2 mutations were detected from 22 pediatric patients with FSGS to establish a test sensitivity of 93%. This screen then was applied to 87 adult patients with idiopathic FSGS (15 steroid-sensitive, 63 steroid-resistant, and nine familial cases). In this latter cohort, compound heterozygous mutations were detected only in one patient with steroid-sensitive FSGS (R229Q and Q285fsX302) and no homozygous mutations. Overall, R229Q accounted for eight (80%) of ten of the putative mutant alleles that were detected in the study cohort. Contrary to the pediatric experience, recessive NPHS2 mutations are rare in this study population, suggesting that the pathogenesis of FSGS in adults may differ from that in children. These data do not support R229Q as a disease-causing mutation for steroid-resistant FSGS.