Whole-exome sequencing identified a novel mutation of BMPR2 in a Chinese family with pulmonary arterial hypertension

Figures & data

Figure 1. (A) Pedigree of the family affected with pulmonary arterial hypertension. Squares,male family members; circles, female members; closed symbols,affected members; open symbols, unaffected members; arrow, proband. (B) Sanger DNA sequencing chromatogram demonstrating the heterozygosity for a BMPR2 mutation (c.453dupA, p.I152Nfs*29).

Table 1. The clinical data of the patient.

	Diagnosis time
Variables	2016.11	2018.11
age,yrs	30	32
heart rate	96 beats/min	81 beats/min
blood pressure	104/77 mmHg	94/70 mmHg
mPAP	68 mmHg	79 mmHg
PAB	29 mm	34 mm
right atrium	54 mm	55 mm
right ventricle	50 mm	52 mm
left atrium	29 mm	30 mm
left ventricle	36 mm	35 mm
degree of blood oxygen saturation
right upper limb	98%	90%
left upper limb	90%	94%
right lower limb	85%	89%
left lower limb	82%	93%
UA	521.7 µmol/L	612.1 µmol/L
TSH	10.27 µIU/mL	9.51 µIU/mL
NT-proBNP	4032.71 pg/mL	2710.47 pg/mL

Notes: mPAP, mean pulmonary arterial pressure; PAB, pulmonary artery broadening; UA, uric acid (reference value: 155.0–357.0 µmol/L); TSH, thyroid-stimulating hormone (reference value: 0.3–4.4 µIU/mL); NT-proBNP, N-terminal pro-brain natriuretic peptide (reference value: <250.00 pg/mL).

Table 2. The gene list after whole-exome sequencing data filtration of the patient.

CHR	POS	REF	ALT	Gene	Mutation	MAF in gnomAD	SIFT	MutationTaster	OMIM	ACMG
2	179403454	C	G	TTN	NM_001267550: exon354:c.G99102C: p.W33034C	0.00006	0.039,D	0.99999,D	AD, Cardiomyopathy	US
2	203378475	T	TA	BMPR2	NM_001204: exon4:c.453dupA: p.I152fs	–	–	1,D	AD,Pulmonary hypertension	PS
4	1807569	G	A	FGFR3	NM_000142: exon13:c.G1738A: p.D580N	–	0.392,T	0.99999,D	AD,Achondroplasia	BP
5	59189182	C	T	PDE4D	NM_001104631: exon1:c.G268A: p.A90T	0.00018	0.006,D	0.95,P	AD, Acrodysostosis	BP
7	128483506	G	A	FLNC	NM_001458: exon18:c.G2686A: p.G896R	0.00041	0.001,D	0.99999,D	AD, Cardiomyopathy	US
9	137726817	C	A	COL5A1	NM_000093: exon65:c.C5137A: p.L1713I	–	0.600,T	0.99990,D	AD, Ehlers-Danlos syndrome	BP
12	6094770	C	T	VWF	NM_000552: exon39:c.G6860A: p.R2287Q	0.00051	0.393,T	0.9588,D	AD, von Willebrand disease	BP
16	50753909	C	A	NOD2	NM_022162: exon7:c.C2704A: p.Q902K	0.00038	0.310,T	0.99999,D	AD, Blau syndrome	BP
19	15281580	T	A	NOTCH3	NM_000435: exon26:c.A4793T: p.D1598V	0.00006	0.069,T	0.99943,D	AD, Lateral meningocele syndrome	BP

Notes: CHR, Chromosome; POS, position; REF, reference sequence base; ALT, alternative base identified; AD, autosomal dominant; P, polymorphism; D, damaging; T, tolerated; ACMG: The American College of Medical Genetics and Genomics classification; PS, pathogenic strong; BP, benign supporting; US, uncertain significance.

Figure 2. Reported mutations of BMPR2 exon 4, red words stands for present study.

Data availability statement

Due to patient privacy, additional supporting data, including genetic data is not available.