Pulmonary arterial hypertension

Gene: SMAD9

Green List (high evidence)

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: SMAD9; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 6 Dec 2018, 2:01 p.m.

In PMID: 20301658 it was noted that most heritable PAH (75%) is caused by a pathogenic variant in BMPR2; pathogenic variants in other genes (i.e., ACVRL1, KCNK3, CAV1, SMAD9, BMPR1B,) are considerably less common (1-3%). In PMID: 21898662 candidate gene analysis was undertaken, members of the bone morphogenetic protein (BMP) pathway, namely SMAD1, SMAD4 and SMAD9, were screened by direct sequencing for gene defects. Four variants were identified among a cohort of 324 PAH cases. In PMID: 24355637 it was noted that SMAD9 variants are more compelling, because these data are supported by the development of clinical and histopathological features of pulmonary hypertension in a Smad9 knock-out mouse model (PMID:19419974). There have been at least three independent cases reported for HPAH caused by SMAD9 variant (PMID:19211612;21898662,21920918).

Created: 9 Jun 2017, 2:12 p.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; Pulmonary arterial hypertension

Publications

• 24355637