Pulmonary arterial hypertension

Gene: CAV1

I don't know

From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : agreed that LCCNS unlikely to present as non-syndromic PPHT so should remain amber

Created: 21 Jan 2019, 5:41 p.m.

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: CAV1; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: Severe infantile syndrome, PAH unlikely to be presenting feature; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 6 Dec 2018, 2:01 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.

Comment on publications: added publication suggested by A.Tucci PMID:27717241, which describes a mutation causing PAH and lipodystrophy, but recommenced by clinical team it is still not enough evidence to make this gene Green, so keep Amber for now.

Created: 22 Jun 2017, 8:14 a.m.

Two unrelated cases PMID:22474227 genetic analysis of an additional patient in the family supported the conclusion that a rare mutation in the CAV1 gene was of pertinence to disease since the observed mutation in exon 3 (c.474delA; p.L159Sfs*22), impacts a highly conserved region and predicts deleterious functional consequences. PMID:25917481 (2015) notes "The SMAD9 and CAV1 were reported as rare nucleotide changes in the exome sequencing project and could thus be regarded as likely non-pathogenic variants" (author statement only). However, it there are Cav1 knockout mice that develop pulmonary hypertension (PMID:12177436, 19419974), supporting the pathogenicity of the variants identified by Austin et al. (2012). PMID: 20301658 notes 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%).

Created: 9 Jun 2017, 2:03 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

• 22474227