Pulmonary arterial hypertension

Gene: SMAD4

Red List (low evidence)

Comment on phenotypes: added PAH

Created: 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.

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

• 24355637
• 21898662