title: Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis.
abstract: 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 S4 voltage-sensing transmembrane segment of the alpha1 subunit of the calcium channel gene (Cav1.1).
  
  
  METHODS
  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.
  
  
  METHODS
  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 small middle dot5 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 S4 voltage-sensing transmembrane segments of Cav1 small middle dot1 (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Laboratory of Molecular Endocrinology, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Magnus R
authors.initials: MR
authors.lastname: Dias da Silva
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
authors.forename: Célia H
authors.initials: CH
authors.lastname: Tengan
authors.forename: Gilberto K
authors.initials: GK
authors.lastname: Furuzawa
authors.forename: Teresa C A
authors.initials: TC
authors.lastname: Vieira
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gabbai
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
mesh_terms: D000328:Adult; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D020514:Hypokalemic Periodic Paralysis / Q000097:blood / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D013963:Thyroid Hormones / Q000097:blood; D013971:Thyrotoxicosis / Q000235:genetics*
chemical_list: D020746:Calcium Channels, L-Type; D013963:Thyroid Hormones