A rare TNNT1 gene variant causing creatine kinase elevation in nemaline myopathy: c.271_273del (p.Lys91del)
Springer Science and Business Media LLC - Trang 1-8 - 2024
Tóm tắt
Nemaline Myopathy (NM) is a rare genetic disorder that affects muscle function and is characterized by the presence of nemaline rods in muscle fibers. These rods are abnormal structures that interfere with muscle contraction and can cause muscle weakness, respiratory distress, and other complications. NM is caused by variants in several genes, including TNNT1, which encodes the protein troponin T1. NM is inherited in an autosomal recessive pattern. The prevalence of heterozygous TNNT1 variants has been reported to be 1/152,000, indicating that the disease is relatively rare. Investigation of TNNT1 gene variants that may cause cretin kinase elevation. Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and family segregation was done by Sanger sequencing. In this study, we report a 5-year-old girl with a novel variant recessive congenital TNNT1 myopathy. The patient had a novel homozygous (c.271_273del) deletion in the TNNT1 gene that is associated with creatine kinase elevation, which is a marker of muscle damage. This case expands the phenotypic spectrum of TNNT1 myopathy and highlights the importance of genetic testing and counseling for families affected by this rare disorder. In this study provides valuable insights into the genetic basis of NM and highlights the importance of early diagnosis and management for patients with this rare disorder. Further research is needed to better understand the pathophysiology of TNNT1 myopathy and to develop effective treatments for this debilitating condition.
Tài liệu tham khảo
Abdulhaq UN, Daana M, Dor T, Fellig Y, Eylon S, Schuelke M, Shaag A et al (2016) Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1). Muscle Nerve 53:564–569. https://doi.org/10.1002/mus.24885
Baris S, Yavas C, Balasar Ö, Gordu Z, Dogan M, Eroz R (2023) Batı Ege Bölgesinde α-Talasemi genotipleri ve α-Talasemi Genotip Frekansı. Sağlık Bilimlerinde Değer 13:257–262
Clayton JS, McNamara EL, Goullee H, Conijn S, Muthsam K, Musk GC, Coote D et al (2020) Ovine congenital progressive muscular dystrophy (OCPMD) is a model of TNNT1 congenital myopathy. Acta Neuropathol Commun 8:142. https://doi.org/10.1186/s40478-020-01017-1
D’Amico A, Fattori F, Fiorillo C, Paglietti MG, Testa MBC, Verardo M, Catteruccia M et al (2019) Amish nemaline myopathy’ in 2 Italian siblings harbouring a novel homozygous mutation in Troponin-I gene. Neuromuscul Disord 29:766–770. https://doi.org/10.1016/j.nmd.2019.09.005
Dahlstedt AJ, Katz A, Wieringa B, Westerblad H (2000) Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase. FASEB J 14:982–990. https://doi.org/10.1096/fasebj.14.7.982
Doğan M, Gezdirici A, Yavaş C, Recep E (2022) Tekrarlayan gebelik kayıpları nedeniyle çalışılan 306 çiftin kromozom analizi ve trombofili parametrelerinin değerlendirilmesi: tek merkez deneyimi. Sağlık Bilimlerinde Değer 12:280–285
Doğan M, Akbulut E, Gezdirici A, Eroz R, Bozdoğan ST (2023) Bialelic pathogenic (c. 830G > A (p. R277Q)) variant disrupting the GNE gene function and causes Nonaka myopathy phenotype. Cytol Genet 57:347–355
Fattahi Z, Kalhor Z, Fadaee M, Vazehan R, Parsimehr E, Abolhassani A, Beheshtian M et al (2017) Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population. Clin Genet 91:386–402. https://doi.org/10.1111/cge.12810
Fox MD, Carson VJ, Feng HZ, Lawlor MW, Gray JT, Brigatti KW, Jin JP et al (2018) TNNT1 nemaline myopathy: natural history and therapeutic frontier. Hum Mol Genet 27:3272–3282. https://doi.org/10.1093/hmg/ddy233
Geraud J, Dieterich K, Rendu J, Uro Coste E, Dobrzynski M, Marcorelle P, Ioos C et al (2021) Clinical phenotype and loss of the slow skeletal muscle troponin T in three new patients with recessive TNNT1 nemaline myopathy. J Med Genet 58:602–608. https://doi.org/10.1136/jmedgenet-2019-106714
Gezdirici A, İli EG, Değirmenci B, Gümüş AA, Özdemir G, Erman NA, Yavaş C (2021) Hereditary breast-ovarian cancer and BRCA1/BRCA2 variants: a single center experience. Acta Oncol Turc 54:264–272
Johnston JJ, Kelley RI, Crawford TO, Morton DH, Agarwala R, Koch T, Schaffer AA et al (2000) A novel nemaline myopathy in the amish caused by a mutation in troponin T1. Am J Hum Genet 67:814–821. https://doi.org/10.1086/303089
Konersman CG, Freyermuth F, Winder TL, Lawlor MW, Lagier-Tourenne C, Patel SB (2017) Novel autosomal dominant TNNT1 mutation causing nemaline myopathy. Mol Genet Genomic Med 5:678–691. https://doi.org/10.1002/mgg3.325
Lee S, Eum J, Park S, Ki S, Hwang BJ, Kee Y, Chae JH (2022) TNNT1 myopathy with novel compound heterozygous mutations. Neuromuscul Disord 32:176–184. https://doi.org/10.1016/j.nmd.2021.12.003
Marra JD, Engelstad KE, Ankala A, Tanji K, Dastgir J, De Vivo DC, Coffee B et al (2015) Identification of a novel nemaline myopathy-causing mutation in the troponin T1 (TNNT1) gene: a case outside of the old order amish. Muscle Nerve 51:767–772. https://doi.org/10.1002/mus.24528
Mondal A, Jin JP (2016) Protein structure-function relationship at work: learning from myopathy mutations of the slow skeletal muscle isoform of troponin T. Front Physiol 7:449. https://doi.org/10.3389/fphys.2016.00449
Pellerin D, Aykanat A, Ellezam B, Troiano EC, Karamchandani J, Dicaire MJ, Petitclerc M et al (2020) Novel recessive TNNT1 congenital core-rod myopathy in French canadians. Ann Neurol 87:568–583. https://doi.org/10.1002/ana.25685
Pergande M, Motameny S, Ozdemir O, Kreutzer M, Wang H, Daimaguler HS, Becker K et al (2020) The genomic and clinical landscape of fetal akinesia. Genet Med 22:511–523. https://doi.org/10.1038/s41436-019-0680-1
Petrucci A, Primiano G, Savarese M, Sancricca C, Udd B, Servidei S (2021) Novel TNNT1 mutation and mild nemaline myopathy phenotype in an Italian patient. Neuromuscul Disord 31:532–538. https://doi.org/10.1016/j.nmd.2021.03.001
Sato T, Ito Y, Nagasawa T (2013) Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats. J Nutr Sci Vitaminol (Tokyo) 59:412–419. https://doi.org/10.3177/jnsv.59.412
Silva LHP, Rodrigues RTS, Assis DEF, Benedeti PDB, Duarte MS, Chizzotti ML (2019) Explaining meat quality of bulls and steers by differential proteome and phosphoproteome analysis of skeletal muscle. J Proteom 199:51–66. https://doi.org/10.1016/j.jprot.2019.03.004
Streff H, Bi W, Colon AG, Adesina AM, Miyake CY, Lalani SR (2019) Amish nemaline myopathy and dilated cardiomyopathy caused by a homozygous contiguous gene deletion of TNNT1 and TNNI3 in a mennonite child. Eur J Med Genet 62:103567. https://doi.org/10.1016/j.ejmg.2018.11.001
Takagi Y, Yasuhara T, Gomi K (2001) Creatine kinase and its isozymes. Rinsho Byori Suppl 116:52–61
Turner D, Eppenberger H (2019) Developmental changes in creatine kinase and aldolase isoenzymes and their possible function in association with contractile elements. Enzyme Protein 15:224–238
van der Pol WL, Leijenaar JF, Spliet WG, Lavrijsen SW, Jansen NJ, Braun KP, Mulder M et al (2014) Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree. Mol Genet Genomic Med 2:134–137. https://doi.org/10.1002/mgg3.52
Wang G, Zhao D, Yan C, Lin P (2023) Exon skipping caused by splicing mutation in TNNT1 nemaline myopathy. J Hum Genet 68:97–101. https://doi.org/10.1038/s10038-022-01096-z
Yamashita S, Nagatoshi A, Takeuchi Y, Nishino I, Ueda M (2023) Myopathic changes caused by protein aggregates in adult-onset spinal muscular atrophy. Neuropathology https://doi.org/10.1111/neup.12901
Yavas C, Un C, Celebi E, Gezdirici A, Dogan M, Ili EG, Dogan T et al (2022) Whole-exome sequencing (WES) results of 50 patients with chronic kidney diseases: a perspective of Alport syndrome. Rev Assoc Med Bras (1992) 68:1282–1287. https://doi.org/10.1590/1806-9282.20220405
Zambon AA, Abel F, Linnane B, O’Rourke D, Phadke R, Sewry CA, Sarkozy A et al (2022) Troponin-T type 1 (TNNT1)-related nemaline myopathy: unique respiratory phenotype and muscle pathology findings. Neuromuscul Disord 32:245–254. https://doi.org/10.1016/j.nmd.2022.01.014