Centronuclear myopathy with cardiomyopathy due to recessive titinopathy

Martinez‐Thompson, Jennifer M.; Winder, Thomas; Liewluck, Teerin

doi:10.1002/mus.26429

Cited by 3 publications

(3 citation statements)

References 7 publications

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“…In the current study, we found that fiber size variation, muscle fiber hypertrophy or atrophy, and centralized nuclei were the most common histopathological features. Mutations in TTN were also found to cause congenital myopathies, such as core myopathy and centronuclear myopathy 23–25 . In our research, patient 4 was histologically diagnosed as having core myopathy.…”

Section: Discussionmentioning

confidence: 51%

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Clinicopathological features of titinopathy from a Chinese neuromuscular center

Huang

Duan

et al. 2021

Neuropathology

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Titin, one of the largest proteins in humans, is a major component of muscle sarcomeres. Pathogenic variants in the titin gene (TTN) have been reported to cause a range of skeletal muscle diseases, collectively known as titinopathy. Titinopathy is a heterogeneous group of disabling diseases characterized by muscle weakness. In our study, we aimed to establish the clinicopathologicalgenetic spectrum of titinopathy from a single neuromuscular center. Three patients were diagnosed as having definite titinopathy, and additional three patients were diagnosed as having possible titinopathy according to the diagnostic criteria. All the patients showed initial symptoms from age one to 40 years. Physical examination revealed that five patients had muscle weakness, and that one patient experienced behavioral changes. Muscle biopsy specimens obtained from all six patients demonstrated multiple myopathological changes, including increased fiber size variation, muscle fiber hypertrophy or atrophy, formation of centralized cell nuclei, necklace cytoplasmic bodies, and formation of rimmed vacuoles and cores. Genetic testing revealed 11 different TTN alterations, including missense (6/11), nonsense (2/11), frameshift (2/ 11), and splicing (1/11) mutations. Our study provides further evidence that TTN mutations are more likely to be responsible for an increasing proportion of various myopathies, such as hereditary myopathy with early respiratory failure (HMERF), core myopathy, and distal myopathy with rimmed vacuoles, than currently recognized mutations. Our findings expand the clinical, pathohistological and genetic spectrum of titinopathy.

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Section: Discussionmentioning

confidence: 51%

“…Mutations in TTN were also found to cause congenital myopathies, such as core myopathy and centronuclear myopathy. [23][24][25] In our research, patient 4 was histologically diagnosed as having core myopathy. We also found that the phenotypes of patients 1 and 2 were consistent with HMERF, a common subtype of titinopathy.…”

Section: Discussionmentioning

confidence: 77%

Clinicopathological features of titinopathy from a Chinese neuromuscular center

Huang

Duan

et al. 2021

Neuropathology

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“…In a recent report, a 54-year-old female with a recessively inherited TTN-centronuclear myopathy, was diagnosed at her 35 with dilated cardiomyopathy and presented muscle weakness many years later. She had some skeletal manifestations (scoliosis and achilles tendon contractures) since childhood, but the full-blown clinical picture developed in adulthood, implying that TTN-related cardiomyopathy may manifest at any age and routine monitoring is always crucial for these patients [190]. Overall, titin is a giant protein encoded by a large gene and the interpretation of pathogenicity of genetic variants remains a great challenge.…”

Section: Titin-related Myopathiesmentioning

confidence: 99%

Update on Congenital Myopathies in Adulthood

Papadimas

Xirou

Kararizou

et al. 2020

IJMS

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Congenital myopathies (CMs) constitute a group of heterogenous rare inherited muscle diseases with different incidences. They are traditionally grouped based on characteristic histopathological findings revealed on muscle biopsy. In recent decades, the ever-increasing application of modern genetic technologies has not just improved our understanding of their pathophysiology, but also expanded their phenotypic spectrum and contributed to a more genetically based approach for their classification. Later onset forms of CMs are increasingly recognised. They are often considered milder with slower progression, variable clinical presentations and different modes of inheritance. We reviewed the key features and genetic basis of late onset CMs with a special emphasis on those forms that may first manifest in adulthood.

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The constantly evolving spectrum of phenotypes in titinopathies – will it ever stop?

Udd

2020

Current Opinion in Neurology

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Purpose of review The last few years have confirmed previous assumptions of an enormous impact of the titin gene (TTN) on the occurrence of muscle disease, cardiomyopathy, or both together. The reason for this rather late understanding of its importance is because of the huge size which prevented sequencing of the whole gene by the previous Sanger technique in the individual cases. An update of the advances in diagnosing titinopathies is the main focus of this review. Recent findings High throughput methods are now widely available for TTN sequencing and a corresponding explosion of different types of identified titinopathies is observed and published in the literature, although final confirmation is lacking in many cases with recessive missense variants. Summary The implications of these findings for clinical practice are easy to understand: patients with previously undiagnosed muscle disease can now have a correct diagnosis and subsequently receive a likely prognosis, can have accurate genetic counseling for the whole family and early treatment for predictable complications from the heart and respiratory muscles. In addition not to forget, they can avoid wrong diagnoses leading to wrong treatments.

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Centronuclear myopathy with cardiomyopathy due to recessive titinopathy

Cited by 3 publications

References 7 publications

Clinicopathological features of titinopathy from a Chinese neuromuscular center

Clinicopathological features of titinopathy from a Chinese neuromuscular center

Update on Congenital Myopathies in Adulthood

The constantly evolving spectrum of phenotypes in titinopathies – will it ever stop?

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