Variable cardiovascular phenotypes associated with SMAD2 pathogenic variants

Human Mutation
Jorge L GranadilloMarwan Shinawi

Abstract

SMAD2 is a downstream effector in the TGF-β signaling pathway, which is important for pattern formation and tissue differentiation. Pathogenic variants in SMAD2 have been reported in association with arterial aneurysms and dissections and in large cohorts of subjects with complex congenital heart disease (CHD). We used whole exome sequencing (WES) to investigate the molecular cause of CHD and other congenital anomalies in three probands and of an arterial aneurysm in an additional patient. Patients 1 and 2 presented with complex CHD, developmental delay, seizures, dysmorphic features, short stature, and poor weight gain. Patient 3 was a fetus with complex CHD and heterotaxy. The fourth patient is an adult female with aortic root aneurysm and physical features suggestive of a connective tissue disorder. WES identified pathogenic truncating variants, a splice variant, and a predicted deleterious missense variant in SMAD2. We compare the phenotypes and genotypes in our patients with previously reported cases. Our data suggest two distinct phenotypes associated with pathogenic variants in SMAD2: complex CHD with or without laterality defects and other congenital anomalies, and a late-onset vascular phenotype characterized by arteri...Continue Reading

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Citations

Jan 5, 2019·Current Opinion in Obstetrics & Gynecology·Fengchang QiaoZhengfeng Xu
Dec 27, 2019·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Shannon N Nees, Wendy K Chung
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Dec 19, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiaominting SongJin Pei
Apr 20, 2021·Mediators of Inflammation·Yi-Ling WenSi Qin
Jul 31, 2021·Circulation. Genomic and Precision Medicine·Miriam S ReuterAnne S Bassett
Aug 7, 2021·American Journal of Medical Genetics. Part a·Alanna StrongReed E Pyeritz

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