De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.
Smooth muscle cells (SMCs) contract to perform many physiological functions, including regulation of blood flow and pressure in arteries, contraction of the pupils, peristalsis of the gut, and voiding of the bladder. SMC lineage in these organs is characterized by cellular expression of the SMC isoform of α-actin, encoded by the ACTA2 gene. We report here on a unique and de novo mutation in ACTA2, R179H, that causes a syndrome characterized by dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.
Milewicz
Dianna M
DM
Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. dianna.m.miledwicz@uth.tmc.edu
Østergaard
John R
JR
Ala-Kokko
Leena M
LM
Khan
Nadia
N
Grange
Dorothy K
DK
Mendoza-Londono
Roberto
R
Bradley
Timothy J
TJ
Olney
Ann Haskins
AH
Adès
Lesley
L
Maher
Joseph F
JF
Guo
Dongchuan
D
Buja
L Maximilian
LM
Kim
Dong
D
Hyland
James C
JC
Regalado
Ellen S
ES
D000199:Actins / Q000235:genetics*; D000293:Adolescent; D000784:Aortic Dissection / Q000235:genetics / Q000601:surgery; D000818:Animals; D001011:Aorta / Q000473:pathology; D001014:Aortic Aneurysm / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009154:Mutation; D020125:Mutation, Missense; D014652:Vascular Diseases / Q000235:genetics* / Q000601:surgery
C541116:ACTA2 protein, human; D000199:Actins