Extending the clinical and mutational spectrum of<i>TRIM32</i>-related myopathies in a non-Hutterite population

Johnson, Katherine; Ridder, Willem De; Töpf, Ana; Bértoli, Marta; Phillips, Lauren; Jonghe, Peter De; Baets, Jonathan; Deconinck, Tine; Stojanović, Vidosava Rakočević; Perić, Stojan; Durmuş, Hacer; Jamal-Omidi, Shirin; Nafissi, Shahriar; Mongini, Tiziana; Łusakowska, Anna; Busby, Mark; Miller, James; Norwood, Fiona; Hudson, Judith A.; Barresi, Rita; Lek, Monkol; MacArthur, Daniel G.; Straub, Volker

doi:10.1136/jnnp-2018-318288

Cited by 11 publications

(17 citation statements)

References 5 publications

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“…The participating centers provided consent for data sharing facilitated by the European Genome-Phenome Archive (EGA) and RD-Connect (https://platform.rd-connect.eu/), and we advocate that adopting such an approach will enable future matchmaking between extremely rare cases, such as BVESrelated myopathy 34 or LGMD R21 POGLUT1-related. 35 In addition, thanks to the large cohort size and standardized deep phenotypic data, we were able to expand the clinical and mutational spectrum of known causative genes, such as TRIM32, 36 POMK, 37 DPM3, 38 POMT2, 39 and other dystroglycanopathies. 40 Based on our findings from this large-scale international collaboration, we suggest a new diagnostic approach in the clinic and/or private health providers.…”

Section: Discussionmentioning

confidence: 99%

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Töpf

Johnson

Bates

et al. 2020

Genetics in Medicine

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Purpose: Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Methods: Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. Results: We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining wellcharacterized unsolved patients (48%) need further investigation. Conclusion: Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes.

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Section: Discussionmentioning

confidence: 99%

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Töpf

Johnson

Bates

et al. 2020

Genetics in Medicine

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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%

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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“…In addition to the control of the myogenic transcription factors, the UPS can regulate SC function at different levels. As an example, mutations in the gene coding for the RING- E3 ligase Tripartite motif-containing protein 32 (TRIM32) are associated with limb-girdle muscular dystrophy 2H (LGMD2H) and sarcotubular myopathy (STM) ( Frosk et al, 2002 ; Johnson et al, 2019 ). Recently, Servián-Morilla and cols ( Servián-Morilla et al, 2019 ) studied primary myoblasts obtained from patients diagnosed with a form of muscular dystrophy and carried different mutations in the TRIM32 gene (resulting in reduced levels of TRIM32 protein).…”

Section: Ups and The Regulation Of Satellite Cell Functionmentioning

confidence: 99%

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

Olguín

2022

Front. Cell Dev. Biol.

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In recent years, the ubiquitin-proteasome system (UPS) has emerged as an important regulator of stem cell function. Here we review recent findings indicating that UPS also plays critical roles in the biology of satellite cells, the muscle stem cell responsible for its maintenance and regeneration. While we focus our attention on the control of key transcriptional regulators of satellite cell function, we briefly discuss early studies suggesting the UPS participates more broadly in the regulation of satellite cell stemness and regenerative capacity.

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Extending the clinical and mutational spectrum ofTRIM32-related myopathies in a non-Hutterite population

Cited by 11 publications

References 5 publications

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

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

The Gentle Side of the UPS: Ubiquitin-Proteasome System and the Regulation of the Myogenic Program

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