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Abstract Details

A Novel Homozygous TRIM32 Mutation in a Non-Hutterite Patient with Limb-Girdle Muscular Dystrophy
Neuromuscular and Clinical Neurophysiology (EMG)
P15 - Poster Session 15 (12:00 PM-1:00 PM)
1-013
To report a novel TRIM32 mutation in a non-Hutterite patient.
TRIM32 encodes an E3 ubiquitin ligase, tripartite motif-containing protein 32. Recessive TRIM32 mutations cause a muscle-specific phenotype [limb girdle muscular dystrophy (LGMD) and sarcotubular myopathy], a multisystem ciliopathy without muscle involvement (Bardet-Biedl syndrome), or a combination of both phenotypes. TRIM32-LGMD is the most common muscular dystrophy in the Hutterite population due to a founder mutation and has been reported only in few non-Hutterite patients
We reviewed the clinical and laboratory features of a non-Hutterite LGMD patient carrying a novel TRIM32 pathogenic variant. 
A 37-year-old Arab man, whose parents are first degree cousins, presented with a 7-year history of progressive lower limb weakness. Examination showed symmetric proximal weakness affecting lower (MRC grade 1- 2) more than upper limb (MRC grade 3) muscles, along with mild ankle contractures. Creatine kinase was 958 U/L (normal <308U/L). Electromyography revealed a chronic diffuse myopathic process with fibrillation potentials. Repetitive nerve stimulation showed no decrement. Cardiopulmonary evaluation was normal. Triceps biopsy showed dystrophic features without vacuoles. Next generation sequencing of 94 myopathy-causative genes identified: 1) a novel homozygous pathogenic variant (c.758delG)  in TRIM32 leading to premature termination of the protein (p.Leu253Hisfs*31) and disruption of its C-terminal NHL domains; 2) a heterozygous duplication of exons 1-2 of DNM2. A chromosomal microarray confirmed a 68-kb duplication at 19p13.2, including complete duplication of QTRT1 and MIR638, and partial duplication of ILF3 and DNM2.  Additional review of the muscle biopsy slides showed a moderate increase of internalized nuclei but  no radial arrangement of the sarcoplasmic strands, as often seen in DNM2-myopathy.
We report a novel truncating mutation in TRIM32, causing LGMD in an Arab man. The partial duplication of DNM2 without myopathological correlate is of uncertain clinical significance at this time. 
Authors/Disclosures
Pritikanta Paul, MD (University of California, San Francisco)
PRESENTER 		The institution of Dr. Paul has received research support from ZS Associates.
Margherita Milone, MD, FÂ鶹´«Ã½Ó³»­ (Mayo Clinic) Dr. Milone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian Therapeutics. Dr. Milone has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology Genetics, Â鶹´«Ã½Ó³»­. The institution of Dr. Milone has received research support from Mayo Clinic, CCaTS-CBD. The institution of Dr. Milone has received research support from Mayo Clinic, SGP Award. The institution of Dr. Milone has received research support from MDA for Care Center grant. The institution of Dr. Milone has received research support from Regenerative medicine Minnesota.
Jennifer A. Tracy, MD (Mayo Clinic) Dr. Tracy has nothing to disclose.
Teerin Liewluck, MD, FÂ鶹´«Ã½Ó³»­ (Department of Neurology, Mayo Clinic) Dr. Liewluck has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta Therapeutics. Dr. Liewluck has received publishing royalties from a publication relating to health care.