The TRIM32 geno-phenotype spectrum: a Literature Review and 25-year clinical follow-up of two brothers living with sarcotubular myopathy

Objectives. Pathogenic TRIM32 gene variant was first described in 1976 in the Hutterite population of North America, presenting a phenotype of Limb-girdle muscular dystrophy R8 (LGMDR8, formerly termed LGMD2H). In recent years, different pathogenic mutations in this gene have been reported, with a spectrum of phenotypic heterogeneity, causing sarcotubular myopathy (STM), Bardet-Biedl Syndrome (BBS) and scapuloperoneal dystrophy. The genotype-phenotype correlation of this disease has been poorly reported. 

Methods. Here, we perform a literature review to analyze the genotype-phenotype correlation of the pathogenic variants in the TRIM32 gene. We also describe the clinical progression of two cases of STM in two patients presenting the D487N mutation in the TRIM32 gene.

Results. We define the variety of LGMDR8 phenotypes associated with the identified TRIM32 variants so far.

Conclusions. TRIM32 mutations are responsible for a broad spectrum of clinical phenotypes.