Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Table 3 Clinical phenotypes of FBLN2 and PDGFD variant carriers. Sex ratios and mean ± SD diagnostic age and hemodynamic values have been calculated separately for FBLN2 and PDGFD variant carriers

Case ID	Sex	Age_dx (years)	PAH subclass	Ancestry	Gene	MPAP (mmHg)	MPCWP (mmHg)	WHO functional class	Lung tx	Other medical conditions
08-018	F	70	IPAH	EUR	FBLN2	58	14	III	No	HTN, kidney congenital anomaly, Paget’s disease
17-035	F	41	APAH (MCTD)	EAS	FBLN2	43	16	III	No
12-207*	F	44	IPAH	EUR	FBLN2	NA	NA	NA	No	HTN, hypothyroidism
23-001	M	66	IPAH	EUR	FBLN2	68	10	III	No	HTN, OLD (smoker)
29-031	F	57	IPAH	EUR	FBLN2	84	15	NA	No	HTN, mitral valve disease, hypothyroidism, OA, COPD
34-005*	M	69	IPAH	EUR	FBLN2	43	14	NA	No	HTN, CAD
W000210	F	52	IPAH	EUR	FBLN2	75	11	II	No	Hyposplenism
Mean ± SD	2.5:1	53 ± 11				62 ± 17	13 ± 2
W000073*	F	40	IPAH	AFR	PDGFD	73	NA	III	No	PFO, bilateral chronic subdural hematoma, hypothyroidism
JM930	F	2	IPAH	EUR	PDGFD	39	NA	NA	No	Bronchopulmonary dysplasia
E012465	F	55	IPAH	EUR	PDGFD	52	7	III	No	Hypothyroidism, IBS, major depression
E014342*	F	40	IPAH	EUR	PDGFD	57	7	III	No	Emphysema
E014400	F	43	IPAH	EUR	PDGFD	57	4	III	No	Obesity, T2DM
E000844	F	39	IPAH	EUR	PDGFD	51	9	III	No	GERD, asthma, bicornate uterus
13-037	M	43	DTOX	EUR	PDGFD	47	7	II	No	None
23-025*	F	41	IPAH	EUR	PDGFD	64	NA	III	No	Hypothyroidism
E000820	F	73	IPAH	EUR	PDGFD	48	9	II	No	Fatty liver, hypothyroidism, ductal carcinoma, gallstones, superior vena cava and azygos vein thrombosis related to port-a-cath
E010173	F	74	IPAH	EUR	PDGFD	32	9	III	No	MPVD, PVD, obesity, T2DM, HTN, chronic renal impairment, hypothyroidism, OA, hypouricemia, major depression
Mean ± SD	9:1**	50 ± 14				53 ± 12	11 ± 10

*Cases with risk variants in additional PAH risk genes: 12-207 (ABCC8 and GGCX), 34-005 (GGCX), W000073 (TBX4), E014342 (BMPR2), 23-025 (ENG)
**NS, Fisher’s exact test
Abbreviations: CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; GERD, gastrooesophageal reflux disease; HTN, systemic hypertension; IBS, irritable bowel syndrome; MCTD, mixed connective tissue disease; MPVD, mixed pulmonary valve disease; OA, osteoarthritis; OLD, obstructive lung disease; PFO, patent foramen ovale; PVD, peripheral vascular disease; T2DM, type 2 diabetes mellitus

ISSN: 1756-994X