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2.  Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy  
The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most frequent genetic cause of terminal renal failure in the first 3 decades of life. Ten causative genes (NPHP1–NPHP9 and NPHP11), whose products localize to the primary cilia-centrosome complex, support the unifying concept that cystic kidney diseases are “ciliopathies”. Using genome-wide homozygosity mapping, we report here what we believe to be a new locus (NPHP-like 1 [NPHPL1]) for an NPHP-like nephropathy. In 2 families with an NPHP-like phenotype, we detected homozygous frameshift and splice-site mutations, respectively, in the X-prolyl aminopeptidase 3 (XPNPEP3) gene. In contrast to all known NPHP proteins, XPNPEP3 localizes to mitochondria of renal cells. However, in vivo analyses also revealed a likely cilia-related function; suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal. Consistent with a role for XPNPEP3 in ciliary function, several ciliary cystogenic proteins were found to be XPNPEP3 substrates, for which resistance to N-terminal proline cleavage resulted in attenuated protein function in vivo in zebrafish. Our data highlight an emerging link between mitochondria and ciliary dysfunction, and suggest that further understanding the enzymatic activity and substrates of XPNPEP3 will illuminate novel cystogenic pathways.
PMCID: PMC2827951  PMID: 20179356
3.  An Unusual Cause of Paraparesis in a Patient on Chronic Steroid Therapy 
Spinal epidural lipomatosis is the excessive deposition of unencapsulated fat in the epidural space. This is a rare disorder often associated with high levels of endogenous steroids or the administration of exogenous steroids.
Case Description:
A 32-year-old man with congenital kyphosis treated with prednisolone daily for 5 months for interstitial lung disease developed compressive myelopathy.
Magnetic resonance imaging showed congenital kyphosis along with epidural lipomatosis compressing the cord. Cessation of steroid therapy was associated with improvement in the symptoms.
Spinal epidural lipomatosis is a rare side effect of chronic steroid therapy that may occur with relatively short-term, low-dose regimens. In patients with congenital vertebral anomalies, spinal fat deposition may worsen the neurological status in an already compromised cord. Discontinuation of steroid therapy is beneficial; some patients may require surgical intervention for decompression.
PMCID: PMC2032003  PMID: 17385272
Lipomatosis, spinal epidural; Steroid therapy complications; Kyphosis, congenital; Prednisolone; Myelopathy, compressive; Paraparesis; Cushing syndrome

Results 1-3 (3)