Loss of α1β1 Soluble Guanylate Cyclase, the Major Nitric Oxide Receptor, Leads to Moyamoya and Achalasia

被引：97

作者：

Herve, Dominique ^{[1
,2
,3
]}

Philippi, Anne ^{[1
,2
]}

Belbouab, Reda ^{[4
]}

Zerah, Michel ^{[5
]}

Chabrier, Stephane ^{[6
]}

Collardeau-Frachon, Sophie ^{[7
]}

Bergametti, Francoise ^{[1
,2
]}

Essongue, Aurore ^{[1
,2
]}

Berrou, Eliane ^{[8
,9
]}

Krivosic, Valerie ^{[10
]}

Sainte-Rose, Christian ^{[5
]}

Houdart, Emmanuel

Adam, Frederic ^{[8
]}

Billiemaz, Kareen ^{[11
]}

Lebret, Marilyne ^{[8
,9
]}

Roman, Sabine

Passemard, Sandrine ^{[12
,13
]}

Boulday, Gwenola ^{[1
,2
]}

Delaforge, Audrey ^{[14
]}

Guey, Stephanie ^{[1
,2
]}

Dray, Xavier ^{[15
]}

Chabriat, Hugues ^{[1
,2
,3
]}

Brouckaert, Peter ^{[16
]}

Bryckaert, Maryjke ^{[8
,9
]}

Tournier-Lasserve, Elisabeth ^{[1
,2
,14
]}

机构：

[1] INSERM, U1161, F-75010 Paris, France

[2] Univ Paris Diderot, Sorbonne Paris Cite, UMR S1161, F-75010 Paris, France

[3] AP HP, Grp Hosp Saint Louis Lariboisiere Fernand Widal, Ctr Reference Malad Vasc Rares Cerveau & Oeil, Serv Neurol, F-75010 Paris, France

[4] Etab Publ Hosp Hassen Badi el Harrach, Serv Pediat, Algiers 16200, Algeria

[5] AP HP, Grp Hosp Necker Enfants Malades, Serv Neurochirurgie, F-75015 Paris, France

[6] Univ St Etienne Ctr Hosp, Serv Med Phys & Readaptat Pediat, Ctr Natl Reference AVC Enfant,Hop Bellevue, F-42100 St Etienne, France

[7] Hop Mere Enfant, Ctr Pathol Est, F-69500 Lyon, France

[8] INSERM, F-75010 Paris, France

[9] Univ Paris Sud, F-94270 Le Kremlin Bicetre, France

[10] AP HP, Grp Hosp Saint Louis Lariboisiere Fernand Widal, Ctr Reference Malad Vasc Rares Cerveau & Oeil, Serv Ophtalmol, F-75010 Paris, France

[11] Ctr Hospitalier Univ St Etienne, Serv Reanimat Pediat & Neonatal, F-42100 Saint Etienne, France

[12] Univ Lyon 1, Hospices Civils Lyon, Serv Physiol Digest, Hop Edouard Herriot, F-69003 Lyon, France

[13] AP HP, Grp Hosp Robert Debre, Serv Neurope diatrie, F-75019 Paris, France

[14] AP HP, Grp Hosp Saint Louis Lariboisiere Fernand Widal, Ctr Reference Malad Vasc Rares Cerveau & Oeil, Serv Genet Mol Neurovasc, F-75010 Paris, France

[15] AP HP, Grp Hosp Saint Louis Lariboisiere Fernand Widal, Ctr Reference Malad Vasc Rares Cerveau & Oeil, Serv Gastroenterol, F-75010 Paris, France

[16] Univ Ghent, VIB Inflammat Res Ctr, B-9052 Ghent, Belgium

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2014年 / 94卷 / 03期

关键词：

SHEAR-STRESS; DISEASE; DISCOVERY;

D O I：

10.1016/j.ajhg.2014.01.018

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Moyamoya is a cerebrovascular condition characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and the compensatory development of abnormal "moyamoya" vessels. The pathophysiological mechanisms of this condition, which leads to ischemic and hemorrhagic stroke, remain unknown. It can occur as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes). Here, we describe an autosomal-recessive disease leading to severe moyamoya and early-onset achalasia in three unrelated families. This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the alpha 1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO). Platelet analysis showed a complete loss of the soluble alpha 1 beta 1 guanylate cyclase and showed an unexpected stimulatory role of sGC within platelets. The NO-sGC-cGMP pathway is a major pathway controlling vascular smooth-muscle relaxation, vascular tone, and vascular remodeling. Our data suggest that alterations of this pathway might lead to an abnormal vascular-remodeling process in sensitive vascular areas such as ICA bifurcations. These data provide treatment options for affected individuals and strongly suggest that investigation of GUCY1A3 and other members of the NO-sGC-cGMP pathway is warranted in both isolated early-onset achalasia and non-syndromic moyamoya.

引用

页码：385 / 394

页数：10

共 28 条

[11] Spectrum of histopathologic findings in patients with achalasia reflects different etiologies [J].