Affiliation:
1. Clinical Research Center of the University Hospital of the Federal University of Maranhão (CEPEC - HUUFMA), São Luís,Brazil
2. Research Group in Clinical and Molecular Endocrinology and Metabology (ENDOCLIM), São Luís,Brazil
Abstract
Background:
Thyrotoxic Hypokalemic Periodic Paralysis (THPP) is a rare neuromuscular
disease characterized by recurrent episodes of skeletal muscle weakness associated with hypokalemia.
Alterations in protein-encoding genes that are part of ion channels seem to be related to
the development of this disease. However, the pathogenic potential of some variants in these genomic
regions is not yet fully understood. The aim of this study was to screen genetic alterations in
regions coding for calcium (cav1.1), sodium (nav1.4), and potassium (Kir2.6) channels, evaluating
its impact on the phenotype of patients with THPP.
Method:
Four patients with a diagnosis of THPP followed by the Endocrinology Service of the
University Hospital of the Federal University of Maranhão (Brazil) were investigated for the presence
of molecular abnormalities in CACNA1S, SCN4A, and KCNJ18 genes.
Result:
The KCNJ18 analysis revealed at least one polymorphic variant in each patient. Considering
the haplotypic classification of R39Q, R40H, A56E, and I249V variants, two cases were named
Kir2.6_RRAI and the other two patients were named Kir2.6_QHEV. No patient had point mutations
in the regions evaluated for CACNA1S and SCN4A genes.
Conclusion:
The identification of the Kir2.6_RRAI and Kir2.6_QHEV haplotypes reinforces the
existence of two main haplotypes involving these four loci of the KCNJ18gene. On the other hand,
point mutations in CACNA1S, SCN4A, and KCNJ18 genes do not seem to be the main mechanism
of pathogenesis of THPP, indicating that many questions about this topic still remain unclear. So,
the diagnosis of this rare disorder should still be based on clinical and biochemical aspects presented
by the patient.
Publisher
Bentham Science Publishers Ltd.
Subject
Immunology and Allergy,Endocrinology, Diabetes and Metabolism
Cited by
1 articles.
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