Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sampaolo, S.
Right arrow Articles by Di Iorio, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sampaolo, S.
Right arrow Articles by Di Iorio, G.
Neurology 1999;53:1549
© 1999 American Academy of Neurology
Articles

Lack of sodium channel mutation in an Italian family with paramyotonia congenita

S. Sampaolo, MD, A. A. Puca, MD, V. Nigro, MD, V. Cappa, MD, V. Sannino, MD, G. Sanges, MD, V. Bonavita, MD and G. Di Iorio, MD

From Istituto di Scienze Neurologiche (Drs. Sampaolo, Puca, Cappa, Sannino, Sanges, Bonavita, and Di Iorio) and Istituto di Patologia Generale ed Oncologia (Dr. Nigro), Seconda Università degli Studi di Napoli, Naples, Italy.

Address correspondence and reprint requests to Prof. Giuseppe Di Iorio, Istituto di Scienze Neurologiche, Seconda Università degli Studi di Napoli, Via Pansini, 5–80131 Napoli, Italy.

OBJECTIVE: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC).

BACKGROUND: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A, the gene encoding the {alpha}-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found.

METHODS: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene.

RESULTS: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR–single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A.

CONCLUSION: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Key words: Paramyotonia congenita—Sodium channelopathies—SCN4A gene—cDNA analysis.




This article has been cited by other articles:


Home page
 J. Neurol. Neurosurg. PsychiatryHome page
J Kim, Y Hahn, E H Sohn, Y J Lee, J H Yun, J M Kim, and J H Chung
Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica
J. Neurol. Neurosurg. Psychiatry, May 1, 2001; 70(5): 618 - 623.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by AAN Enterprises, Inc.