Do you think CLCN1 Ala493Glu mutation alone (in heterozygosity) could produce the clinical and EMG diagnostic criteria for Myotonia Congenita (Nondystrophic Thomsen's and Becker's Myotonias)? I'm aware previous studies suggested this 8th exon mutation jointly appears with several others. Nevertheless, an (unfinished) study with an Spanish affected family reveals, at least for now, the single c.1478C>A, p.Ala493Glu pathogenic mutation. Interestingly, a 16 months old son of a mildly affected male (belonging to the aforemetioned family) is showing a severe hypotonia (!). Could anybody help me to make some sense out of these data?
Article The Spectrum of CLCN1 Gene Mutations in Patients with Nondys...
Presence of hypotonia speaks against this patient suffering from chloride channel myotonia. Dysfunction of ClC-1 simply does not lend itself to muscular hypoexcitation.
How was this patient's genetic variation identified? Through candidate sequencing of CLCN1, based on family history? It may help to do linkage analysis to ascertain this variant's role in the phenotype.
Since the variation in question has been identified before, but only when other CLCN1 alterations were present as well, it could be that it is not causative, but only modifying the phenotype (or not relevant at all). The paper you cite is unfortunately in Russian.
One thought: myotonic dystrophy (DM), as the name implies, has myotonia as well as hypotonia in its clinical presentation. I am guessing, though, that the myotonia family you mention has no members with obvious DM. Candidate sequencing of
DM genes ZNF9 and DMPK is offered commercially (Athena Diagnostics); it may help rule out DM.
in the pathology of CM no mention of muscular hypotonia, it is also questionable to speak of asthenia despite the frequent muscle hypertrophy; I have a large family affected by CM: two the mutations:R894X (exon 23) and G482R (exon 13) , are you interested for a future collaboration? Manlio Giacanelli
Thanks a lot, Christoph, Frank and Manlio for your valuable responses.
In regards to this future collaboration, Manlio, it seems to be a great chance! Any suggestion about the "logistics"?
Kind regards,
Jaume
as soon as possible I'll send you any suggestions, kind regards, Manlio Giacanelli
Ok Manlio! I was looking forward to your proposal.
Kind regards,
Jaume
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