Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization
Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen fa...
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| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11995 |
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| author | Juliana Gurgel-Giannetti Lucas Santos Souza Guilherme L. Yamamoto Marina Belisario Monize Lazar Wilson Campos Rita de Cassia M. Pavanello Mayana Zatz Umbertina Reed Edmar Zanoteli Acary Bulle Oliveira Vilma-Lotta Lehtokari Erasmo B. Casella Marcela C. Machado-Costa Carina Wallgren-Pettersson Nigel G. Laing Vincenzo Nigro Mariz Vainzof |
| author_facet | Juliana Gurgel-Giannetti Lucas Santos Souza Guilherme L. Yamamoto Marina Belisario Monize Lazar Wilson Campos Rita de Cassia M. Pavanello Mayana Zatz Umbertina Reed Edmar Zanoteli Acary Bulle Oliveira Vilma-Lotta Lehtokari Erasmo B. Casella Marcela C. Machado-Costa Carina Wallgren-Pettersson Nigel G. Laing Vincenzo Nigro Mariz Vainzof |
| author_sort | Juliana Gurgel-Giannetti |
| collection | DOAJ |
| description | Nemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in <i>NEB</i>, five (20%) in <i>ACTA1</i>, two (8%) in <i>KLHL40</i>, and one in <i>TPM2</i> (4%) and <i>TPM3</i> (4%). In the <i>NEB</i>-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of <i>NEB</i> mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation. |
| first_indexed | 2024-03-09T21:36:33Z |
| format | Article |
| id | doaj.art-a584738b8a154bf3a5f440be4bc9ce1d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:36:33Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a584738b8a154bf3a5f440be4bc9ce1d2023-11-23T20:42:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191199510.3390/ijms231911995Nemaline Myopathy in Brazilian Patients: Molecular and Clinical CharacterizationJuliana Gurgel-Giannetti0Lucas Santos Souza1Guilherme L. Yamamoto2Marina Belisario3Monize Lazar4Wilson Campos5Rita de Cassia M. Pavanello6Mayana Zatz7Umbertina Reed8Edmar Zanoteli9Acary Bulle Oliveira10Vilma-Lotta Lehtokari11Erasmo B. Casella12Marcela C. Machado-Costa13Carina Wallgren-Pettersson14Nigel G. Laing15Vincenzo Nigro16Mariz Vainzof17Department of Pediatrics, Service of Neuropediatrics, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, BrazilHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilDepartment of Pediatrics, Service of Neuropediatrics, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, BrazilHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilRede Mater dei de Saúde, Belo Horizonte 30110-062, MG, BrazilHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilDepartamento de Neurologia, Hospital das Clinicas da Universidade de São Paulo (USP), São Paulo 05403-000, SP, BrazilDepartamento de Neurologia, Hospital das Clinicas da Universidade de São Paulo (USP), São Paulo 05403-000, SP, BrazilDepartamento de Neurologia, Hospital São Paulo, Universidade Federal de São Paulo (UNIFESP), São Paulo 04024-002, SP, BrazilFolkhälsan Research Center, Department of Medical Genetics, Medicum, University of Helsinki, 00100 Helsinki, FinlandChildren’s Institute, Hospital das Clínicas HCFMSUP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05508-220, SP, BrazilEscola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador 40110-909, BA, BrazilFolkhälsan Research Center, Department of Medical Genetics, Medicum, University of Helsinki, 00100 Helsinki, FinlandCentre for Medical Research, Queen Elizabeth II Medical Centre, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, WA 6009, AustraliaItaly and Telethon Institute of Genetics and Medicine (TIGEM), Università della Campania Luigi Vanvitelli Napoli, 80078 Pozzuoli, ItalyHuman Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo 05508-220, SP, BrazilNemaline myopathy (NM), a structural congenital myopathy, presents a significant clinical and genetic heterogeneity. Here, we compiled molecular and clinical data of 30 Brazilian patients from 25 unrelated families. Next-generation sequencing was able to genetically classify all patients: sixteen families (64%) with mutation in <i>NEB</i>, five (20%) in <i>ACTA1</i>, two (8%) in <i>KLHL40</i>, and one in <i>TPM2</i> (4%) and <i>TPM3</i> (4%). In the <i>NEB</i>-related families, 25 different variants, 11 of them novel, were identified; splice site (10/25) and frame shift (9/25) mutations were the most common. Mutation c.24579 G>C was recurrent in three unrelated patients from the same region, suggesting a common ancestor. Clinically, the “typical” form was the more frequent and caused by mutations in the different NM genes. Phenotypic heterogeneity was observed among patients with mutations in the same gene. Respiratory involvement was very common and often out of proportion with limb weakness. Muscle MRI patterns showed variability within the forms and genes, which was related to the severity of the weakness. Considering the high frequency of <i>NEB</i> mutations and the complexity of this gene, NGS tools should be combined with CNV identification, especially in patients with a likely non-identified second mutation.https://www.mdpi.com/1422-0067/23/19/11995nemaline myopathynebulinacta1congenital myopathy |
| spellingShingle | Juliana Gurgel-Giannetti Lucas Santos Souza Guilherme L. Yamamoto Marina Belisario Monize Lazar Wilson Campos Rita de Cassia M. Pavanello Mayana Zatz Umbertina Reed Edmar Zanoteli Acary Bulle Oliveira Vilma-Lotta Lehtokari Erasmo B. Casella Marcela C. Machado-Costa Carina Wallgren-Pettersson Nigel G. Laing Vincenzo Nigro Mariz Vainzof Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization International Journal of Molecular Sciences nemaline myopathy nebulin acta1 congenital myopathy |
| title | Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization |
| title_full | Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization |
| title_fullStr | Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization |
| title_full_unstemmed | Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization |
| title_short | Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization |
| title_sort | nemaline myopathy in brazilian patients molecular and clinical characterization |
| topic | nemaline myopathy nebulin acta1 congenital myopathy |
| url | https://www.mdpi.com/1422-0067/23/19/11995 |
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