[Illustrations de La tragique expédition de Lapérouse et Langle] / [Non identifié] ; Vicomte Paul Fleuriot de Langle, aut. du texte

Comprend : [Couverture : le char de Neptune. Bateaux de Lapérouse et de Langle. Carte des terres de Polynésie et d'Australie.] [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [Carte double avant la p.10 de l'Avant-propos :] Voyages de Lapérouse 1785-1788 (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.80 :] J.F. Galaup de Lapérouse (...). P.A. Fleuriot de Langle (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.81 :] Manoir de Rosvilio, près Callac (Côtes-du-Nord) demeure du Chevalier de Langle (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.96 :] Louis XVI donne ses instructions aux chefs de l'expédition (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.97 :] Insulaires et cyclopes de l'île de Paques (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.160 :] Mouillage des frégates françaises devant l'île de Mowee (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.161 :] Costume des habitants de la baie de Langle, manche de Tartarie (.. .). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.192 :] Massacre de MM. De Langle, de Lamanon et de dix autres membres des deux équipages, à Tutuila, Océanie (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008] ; [pl. en reg. p.193 :] Mémorial élevé à Tutuila, en 1887, par les soisn de la Marine française, en souvenir du 11 décembre 1787 (...). [Cote : 16 ° Ln27 85465/Microfilm R 122008]

A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome.

BACKGROUND: The SCN5A gene encodes for the α-subunit of the cardiac sodium channel NaV1.5, which is responsible for the rapid upstroke of the cardiac action potential. Mutations in this gene may lead to multiple life-threatening disorders of cardiac rhythm or are linked to structural cardiac defects. Here, we characterized a large family with a mutation in SCN5A presenting with an atrioventricular conduction disease and absence of Brugada syndrome. METHOD AND RESULTS: In a large family with a high incidence of sudden cardiac deaths, a heterozygous SCN5A mutation (p.1493delK) with an autosomal dominant inheritance has been identified. Mutation carriers were devoid of any cardiac structural changes. Typical ECG findings were an increased P-wave duration, an AV-block I° and a prolonged QRS duration with an intraventricular conduction delay and no signs for Brugada syndrome. HEK293 cells transfected with 1493delK showed strongly (5-fold) reduced Na(+) currents with altered inactivation kinetics compared to wild-type channels. Immunocytochemical staining demonstrated strongly decreased expression of SCN5A 1493delK in the sarcolemma consistent with an intracellular trafficking defect and thereby a loss-of-function. In addition, SCN5A 1493delK channels that reached cell membrane showed gain-of-function aspects (slowing of the fast inactivation, reduction in the relative fraction of channels that fast inactivate, hastening of the recovery from inactivation). CONCLUSION: In a large family, congregation of a heterozygous SCN5A gene mutation (p.1493delK) predisposes for conduction slowing without evidence for Brugada syndrome due to a predominantly trafficking defect that reduces Na(+) current and depolarization force.