Nemaline Myopathy in Brazilian Patients: Molecular and Clinical Characterization

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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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
nemaline myopathy
nebulin
acta1
congenital myopathy
Online Access:https://www.mdpi.com/1422-0067/23/19/11995
Description
Summary: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.
ISSN:1661-6596
1422-0067

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