Pulmonary arterial hypertension
Gene: SMAD4
Comment on phenotypes: added PAHCreated: 1 Oct 2018, 1:38 p.m.
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, 11:59 a.m.
PMID: 26387786 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 variants of unknown significance (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. PAH associations are based on one paper 21898662 (2011) a patient was identified with a putative splice site mutation in SMAD4 which resulted in moderate transcript loss due to compromised splicing efficiency.
Created: 21 Jun 2017, 11:12 a.m.
Phenotypes for gene: SMAD4 were changed from Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050, PAH to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Phenotypes for gene: SMAD4 were changed from Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050 to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050, PAH
Publications for SMAD4 were set to 21898662; 24355637; 26387786; 29650961
Panel reviews were assessed, and panel was revised according to reviews and further in-house curation.
SMAD4 was added to Pulmonary arterial hypertensionpanel. Sources: Expert list
Publications for SMAD4 were set to 21898662; 24355637; 26387786
Publications for SMAD4 were set to 21898662; 24355637; 263877862;26387786
Phenotypes for SMAD4 were set to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
Phenotypes for SMAD4 were set to diopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension;Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050
SMAD4 was added to Pulmonary arterial hypertensionpanel. Sources: Literature
SMAD4 was created by LouiseD