Myoneuropathic presentation of limb girdle muscular dystrophy R8 with a novel TRIM32 mutation

Chandrasekharan, Soumya V.; Sundaram, Soumya; Malaichamy, Sivasankar; Poyuran, Rajalakshmy; Nair, Sruthi S

doi:10.1016/j.nmd.2021.06.003

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…MMRI studies of the lower limbs were described in 49% (26/53) of the cases [our patient; ( 13 , 19 , 21 , 24 – 28 )]. Their images showed fibroadipose degeneration, with preferential affection of the posterior thigh compartment and selective sparing of specific muscles.…”

Section: Resultsmentioning

confidence: 98%

“…To date, 50% (13/26) of the TRIM32 variants ( Table 1 ) considered to be causative for LGMDR8 (when present biallelically, either in homozygosis or in compound heterozygosis) are located in one of the five NHL repeats, like in the case of our patient. However, LGMDR8-causing TRIM32 variants have been recently identified also in non-NHL domains (RING and Coiled-Coil), as well as in the intermediate regions outside the structural domains, like the pre-RING region ( 19 ), inter-CoiledCoil-NHL1 ( 26 ), and inter-NHL3-NHL4 ( 21 ). These findings dismantled the initial hypothesis of a selective involvement of the NHL domains in the LGMDR8 pathogenesis ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

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Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Rimoldi,

Romagnoli,

Magri

et al. 2024

Front. Neurol.

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Limb-girdle muscular dystrophy autosomal recessive 8 (LGMDR8) is a rare clinical manifestation caused by the presence of biallelic variants in the TRIM32 gene. We present the clinical, molecular, histopathological, and muscle magnetic resonance findings of a novel 63-years-old LGMDR8 patient of Italian origins, who went undiagnosed for 24 years. Clinical exome sequencing identified two TRIM32 missense variants, c.1181G > A p.(Arg394His) and c.1781G > A p.(Ser594Asp), located in the NHL1 and NHL4 structural domains, respectively, of the TRIM32 protein. We conducted a literature review of the clinical and instrumental data associated to the so far known 26 TRIM32 variants, carried biallelically by 53 LGMDR8 patients reported to date in 20 papers. Our proband's variants were previously identified only in three independent LGMDR8 patients in homozygosis, therefore our case is the first in literature to be described as compound heterozygous for such variants. Our report also provides additional data in support of their pathogenicity, since p.(Arg394His) is currently classified as a variant of uncertain significance, while p.(Ser594Asp) as likely pathogenic. Taken together, these findings might be useful to improve both the genetic counseling and the diagnostic accuracy of this rare neuromuscular condition.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Rimoldi,

Romagnoli,

Magri

et al. 2024

Front. Neurol.

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“…A patient harboring the TRIM32 D12EfsTer44 (c.35dupA, a single-base-pair insertion in exon 2 of the TRIM32 gene, resulting in a frameshift and premature truncation of 44 residues downstream) mutation present with a waddling gait and slowly progressive weakness of symmetric proximal lower limbs but no respiratory or cardiac symptoms [ 110 ]. In addition, this patient exhibited no weakness in the upper limbs, axial musculature, or cranial muscles.…”

Section: Trim32 and Limb–girdle Muscular Dystrophies (Lgmds)mentioning

confidence: 99%

“…The average peak tension for the grip strength of the forelimb and latency to fall in a wire hang test was decreased by TRIM32-knockout by approximately 17% and 1.8-fold, respectively. Skeletal muscle atrophy and weakness were identified in patients with LGMD2H, as described previously in this review [ 51 , 87 , 88 , 109 , 110 , 113 , 115 ].…”

Section: Animal Models Of Lgmd2hmentioning

confidence: 99%

Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Jeong,

Choi,

Kim

et al. 2023

Cells

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Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb–girdle muscular dystrophy type 2H (LGMD2H). LGMD2H-causing genetic variations of TRIM32 occur most frequently in the C-terminal NHL (ncl-1, HT2A, and lin-41) repeats of TRIM32. LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. Surprisingly, most patients with LGMD2H show minimal or no dysfunction in other tissues or organs, despite the broad expression of TRIM32 in various tissues. This suggests more prominent roles for TRIM32 in skeletal muscle than in other tissues or organs. This review is focused on understanding the physiological roles of TRIM32 in skeletal muscle, the pathophysiological mechanisms mediated by TRIM32 genetic variants in LGMD2H patients, and the correlations between TRIM32 and Duchenne muscular dystrophy (DMD).

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Autosomal Recessive Limb-Girdle Muscular Dystrophies

Tanboon,

Nishino

2023

Current Clinical Neurology

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Myoneuropathic presentation of limb girdle muscular dystrophy R8 with a novel TRIM32 mutation

Cited by 4 publications

References 18 publications

Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Autosomal Recessive Limb-Girdle Muscular Dystrophies

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