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ACTA2 mutation with childhood cardiovascular, auronomic and brain anomalies and severe outcome
- Source :
- American Journal of Medical Genetics Part A, 161A, 1376-1380. Wiley-Liss Inc., American Journal of Medical Genetics A, 161, 1376-1380. Wiley-Liss Inc.
- Publication Year :
- 2013
-
Abstract
- Thoracic aortic aneurysm and dissection (TAAD) are associated with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome, caused by mutations in the fibrillin-1, the TGFβ-receptor 1- and -2 genes, the SMAD3 and TGFβ2 genes, but have also been ascribed to ACTA2 gene mutations in adults, spread throughout the gene. We report on a novel de novo c.535C>T in exon 6 leading to p.R179C aminoacid substitution in ACTA2 in a toddler girl with primary pulmonary hypertension, persistent ductus arteriosus, extensive cerebral white matter lesions, fixed dilated pupils, intestinal malrotation, and hypotonic bladder. Recently, de novo ACTA2 R179H substitutions have been associated with a similar phenotype and additional cerebral developmental defects including underdeveloped corpus callosum and vermis hypoplasia in a single patient. The patient here shows previously undescribed abnormal lobulation of the frontal lobes and position of the gyrus cinguli and rostral dysplasis of the corpus callosum; she died at the age of 3 years during surgery due to vascular fragility and rupture of the ductus arteriosus. Altogether these observations support a role of ACTA2 in brain development, especially related to the arginine at position 179. Although all previously reported patients with R179H substitution successfully underwent the same surgery at younger ages, the severe outcome of our patient warns against the devastating effects of the R179C substitution on vasculature.
- Subjects :
- Marfan syndrome
Heterozygote
congenital, hereditary, and neonatal diseases and abnormalities
Pathology
medicine.medical_specialty
Genotype
Hypertension, Pulmonary
Mutation, Missense
Corpus callosum
Thoracic aortic aneurysm
Corpus Callosum
Aortic aneurysm
Ductus arteriosus
Genetics
medicine
Humans
Missense mutation
Ductus Arteriosus, Patent
Genetic Association Studies
Genetics (clinical)
Aortic Aneurysm, Thoracic
business.industry
Mydriasis
Retinal Vessels
Anatomy
medicine.disease
Actins
Radiography
Cerebrovascular Disorders
Phenotype
medicine.anatomical_structure
Amino Acid Substitution
Frontal lobe
Intestinal malrotation
Child, Preschool
Female
business
Digestive System Abnormalities
Intestinal Volvulus
Subjects
Details
- ISSN :
- 15524825
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....db872d8ead81768fcbee01a37d1b4e04