Renal findings in patients with Mulibrey nanism

Abstract

Genetic defects in the TRIM37 gene lead to an increased risk for kidney anomalies, renal tumors, and solitary cysts in addition to glomerular cystic lesions, but not to progressive deterioration of renal function.

TRIM37 deficiency induces autophagy through deregulating the MTORC1-TFEB axis

“…Our study suggests that autophagy may facilitate a prosurvival function upon the loss of TRIM37. Patients with TRIM37 gene mutations have high risk of developing tumors, with kidneys being the organ that is affected most often [2,[4][5][6][7][8]. Consistently, TRIM37 protein is hardly detected in renal cancers, compared to its high level in normal tissues [52].…”

“…Its gene mutations result in mulibrey (muscleliver-brain-eye) nanism, which is a rare, autosomal-recessive growth disorder of prenatal onset, with characteristic dysmorphic features, pericardial constriction, and hepatomegaly [1,2]. Additionally, patients have high risk of developing insulin resistance, type 2 diabetes, and tumors [2][3][4][5][6][7][8]. So far, 23 TRIM37 gene mutations have been identified in mulibrey nanism patients (the Leiden Open Variation Database, LOVD; http://databases.lovd.nl/shared/genes/TRIM37).…”

Wilms tumour surveillance in at-risk children: Literature review and recommendations from the SIOP-Europe Host Genome Working Group and SIOP Renal Tumour Study Group

“…Mulibrey nanism, caused by biallelic pathogenic TRIM37 variants, has mainly been reported in Finnish patients and is associated with an estimated WT risk of 6e8% [95,96].…”

TRIMming down to TRIM37: Relevance to Inflammation, Cardiovascular Disorders, and Cancer in MULIBREY Nanism

“…The insulin/IGF-1 is controlled by post-translational modifications, including ubiquitination, which declines during aging. Even if most MULIBREY patients have a normal kidney function, structural anomalies of the kidneys and urinary tract are found in 13% of the patients, concomitant with glomerular cysts, thick-walled blood vessels, and an increase in the expression of angiogenesis-related markers PDGF-B and FGF1 [28]. It is well known that long-term diabetes is associated with heart failure [19,29].…”

“…Although TRIM37 mutations lead to an increased risk of tumors [28], this is questionable when considering cancer among non-MULIBREY patients. In several non-MULIBREY cancers, TRIM37 has been found to be overexpressed (Figure 3).…”