Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations in _CLCN_1gene, and can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we describe a 46-year-old male patient affected by myotonia congenita. Genetic analysis identified the mutation p.Val536Ile, and structural analysis suggests a pathological role for this variant. In fact, the presence of a bulky residue in the place of valine 536, such as leucine or isoleucine, may generate interactions with Tyr578, thus altering its function and impairing the dynamics of ion current. A mutation affecting the same aminoacid 536 (p.Val536Leu) has already been described, but in association with a second mutation (p.Phe167Leu). Therefore, these data highlight the importance of establishing the inheritance pattern for each variant of CLCN1 gene, that, joined with phenotype heterogeneity, may improve the diagnosis and genetic counseling in MC patients.

Structural modeling of altered CLCN1 conformation following a novel mutation in a patient affected by autosomal dominant myotonia congenita (Thomsen disease)

Francesco Fornai;
2017

Abstract

Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations in _CLCN_1gene, and can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we describe a 46-year-old male patient affected by myotonia congenita. Genetic analysis identified the mutation p.Val536Ile, and structural analysis suggests a pathological role for this variant. In fact, the presence of a bulky residue in the place of valine 536, such as leucine or isoleucine, may generate interactions with Tyr578, thus altering its function and impairing the dynamics of ion current. A mutation affecting the same aminoacid 536 (p.Val536Leu) has already been described, but in association with a second mutation (p.Phe167Leu). Therefore, these data highlight the importance of establishing the inheritance pattern for each variant of CLCN1 gene, that, joined with phenotype heterogeneity, may improve the diagnosis and genetic counseling in MC patients.
Ferese, Rosangela; Albano, Veronica; Falconi, Mattia; Iacovelli, Federico; Campopiano, Rosa; Scala, Simona; Maria Griguoli, Anna; Gaglione, Anderson; Giardina, Emiliano; Zampatti, Stefania; Storto, Marianna; Fornai, Francesco; D’Alessio, Carmelo; Novelli, Giuseppe; Gambardella, Stefano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/889347
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