Pulmonary arterial hypertension

Gene: SMAD1

Red List (low evidence)

PMID: 29650961 (2018) further question the validity of CAV1, SMAD1 and SMAD4 causing PAH. No pathogenic coding variants in CAV1, SMAD1 or SMAD4 were identified. However it was noted that the participants with causative variants reported in these genes might represent private mutations in in very rare families.

Created: 16 Apr 2018, 12:01 p.m.

PMID: 26387786 (2011) Mutations in the genes encoding the downstream signalling intermediaries for bone morphogenetic protein receptors, the Smad proteins have been reported in some patients with PAH. Of these, the SMAD1 and SMAD4 defects have been described as VUS due to in vitro luciferase SMAD responsive elements reporter assays demonstrating an unclear impact on the canonical pathways (PMID:21898662). However, these analyses did not investigate SMAD-independent pathways, implicated in disease pathogenesis, leaving open the possibility that the identified variants may deleteriously affect other BMP related systems. There is a mouse model PMID:23478097 (2013) where SMAD1 deficiency in either endothelial or smooth muscle cells predisposed mice to pulmonary hypertension.

Created: 21 Jun 2017, 11:15 a.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH

Publications

• 21898662, 24135949