Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha 1 subunit gene (Ca(v)1 center dot 1) are not associated with thyrotoxic hypokalaemic periodic paralysis

• Autor(a) principal: Silva, Magnus R Dias da [UNIFESP]
• Data de Publicação: 2002
• Outros Autores: Cerutti, Janete Maria [UNIFESP], Tengan, Celia Harumi [UNIFESP], Furuzawa, Gilberto Koiti [UNIFESP], Vieira, Teresa C. Alfinito [UNIFESP], Gabbai, Alberto Alain [UNIFESP], Maciel, Rui Monteiro de Barros [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1046/j.1365-2265.2002.01481.x; http://repositorio.unifesp.br/handle/11600/43358

OBJECTIVE To investigate whether patients with thyrotoxic hypokalaemic periodic paralysis (THPP) have the same molecular defect in the calcium channel gene described in familial hypokalaemic periodic paralysis (FHPP), as the symptoms of both diseases are comparable, we analysed, in patients with THPP, the presence of mutations R528H, R1239H and R1239G on the S-4 voltage-sensing transmembrane segment of the alpha1 subunit of the calcium channel gene (Cav1.1).DESIGN AND PATIENTS Genomic DNA was extracted from peripheral blood from 14 patients with THPP, 13 sporadic cases and one with a family history. An FHPP family was selected as a positive control. The exons bearing the described mutations were amplified by PCR, screened by single-strand conformation polymorphism (SSCP), and further sequenced.MEASUREMENTS THPP was diagnosed both clinically and through laboratory tests, all patients having elevated levels of thyroid hormones (T4, T3 or free T4), suppressed TSH and plasma potassium below 3.5 mmol/l.RESULTS No evidence of the described mutations was found in patients with THPP. Furthermore, we did not detect any mutations in any of the four full S-4 voltage-sensing transmembrane segments of Cav1.1 (DIS4, DIIS4, DIIIS4 and DIVS4) by direct sequencing. However, close to the R528H mutation, we identified two single nucleotide polymorphisms at nucleotides 1551 and 1564 in both familial and sporadic cases with THPP. In addition, we were able to detect the R528H mutation in the DIIS4 transmembrane segment in all members of the FHPP family.CONCLUSION Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis. However, polymorphisms in nucleotides 1551 and 1564 in the exon 11 were found in patients with familial hypokalaemic periodic paralysis and thyrotoxic hypokalaemic periodic paralysis in higher frequency than in controls. The polymorphisms identified within the Cav1.1 gene are associated with thyrotoxic hypokalaemic periodic paralysis and represent a novel finding.