Proteinuric renal disease

Region: ISCA-37417-Loss

Xp22.31 recurrent region (includes STS) Loss

Green List (high evidence)

Comment on list classification: There are at least 3 unrelated male individuals with ichthyosis and renal disease including proteinuria, harbouring heterozygous deletions affecting the ISCA-37417-Loss region (particularly full STS deletions). Hence, this region should be promoted to Green at the next update.

Created: 7 Jul 2026, 4:53 p.m. | Last Modified: 7 Jul 2026, 4:53 p.m.

Panel Version: 6.8

PMID: 17468528 Krishnamurthy, Kapoor, and Yadav, 2007
Reported a 4yo proband with ichthyosis and a steroid-resistant nephrotic syndrome. Generalised edema and proteinuria of 4.25g/day were noted. Many male family members also had ichthyosis. Renal biopsy showed no segmental sclerosis, tubular atrophy, fibrosis, or deposits; diagnosed with minimal change disease. STS deletion detected by multiplex PCR (targeted STS gene specifically).

PMID: 22419362 Mishra et al., 2012
Report of a 4yo boy with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Genetic analysis showed full deletion of the STS gene.

PMID: 23939749 Song et al., 2013
12yo male patient with X-linked ichthyosis (XLI) in association with glomerular sclerosis. Complete deletion of STS and flanking regions was detected. Renal features: renal failure, anemia, hypocalcemia, mild proteinuria (0.4g/day). Uncles also affected by ichthyosis and short stature. Authors highlight that it is unknown whether STS or the flanking regions were causal in the renal presentation.

PMID: 29672931 Diociaiuti et al., 2019
Cohort of 35 Italian male patients with X-linked ichthyosis. 27 patients showed complete STS deletion - 1 de novo, others maternally inherited. 7 patients had microdeletions of 1.3-1.6Mb, and 2 patients had large deletions of 8.2 and 9.7Mb - resulting in contiguous gene syndrome. Lastly, 7 individuals from 4 unrelated families had 4 different missense mutations in STS. Seq method: MLPA + ichthyosis NGS panel. Apart from cutaneous changes, other findings included cryptorchidism, neuropsychiatric findings, motor disabilities. No mention of renal disease. Authors note that only 10% of patients have point mutations in STS, with majority of cases harbouring STS deletions.

PMID: 35115028 Schierz et al., 2022
Male newborn with CAKUT with kidney failure and progressive vomiting. "Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene." Other affected genes: VCX, PUDP, PNPLA4, as well as microRNAs MIR4767 and MIR651.
Sources: Literature

Created: 7 Jul 2026, 4:51 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Ichthyosis, X-linked, OMIM:308100

Publications

• 17468528
• 22419362
• 23939749
• 29672931
• 35115028