Paramyotonia congenita : genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene

• Published in: Journal of the neurological sciences 1996-10, Vol.142 (1-2), p.126-133
• Main Authors: PLASSART, E, EYMARD, B, MAURS, L, HAUW, J. J, LYON-CAEN, O, FARDEAU, M, FONTAINE, B
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; Family Health; Female; Genotype; Humans; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Myotonia Congenita - genetics; Neurology; Neuromuscular Junction - chemistry; Pedigree; Phenotype; Point Mutation - physiology; Protein Structure, Tertiary; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Sodium Channels - chemistry; Sodium Channels - genetics
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510x(96)00173-6

Sodium channel disorders include hyperkalemic periodic paralysis (hyperPP), paramyotonia congenita (PC) and potassium-aggravated myotonia (PAM). PC is a myotonic syndrome characterized by cold-induced muscle stiffness and weakness. In this paper, we report two families. The first is affected by PC with cold-induced stiffness and no weakness, in addition to hyperPP. This family displays the Arg1448Cys mutation in the sodium channel gene originally described in pure PC families. The fact that families with the same mutation present distinct phenotypes indicates that other factors, genetic or environmental, may modulate the expression of the disease in sodium channel disorders. The second family was unusual because patients presented cold-induced weakness without stiffness. A mutation was found in the sodium channel gene that changed an isoleucine into a threonine at position 693. These two families demonstrate that sodium channel mutations may cause either cold-induced stiffness or weakness.