Molecular genetics and clinical features of Chinese idiopathic and heritable pulmonary arterial hypertension patients

Abstract

Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene predispose to pulmonary arterial hypertension (PAH). 290 idiopathic (I)PAH patients and 15 heritable (H)PAH were screened to determine the spectrum and rate of BMPR2 mutations in a large Chinese patient group.Gene sequencing and multiplex ligation-dependent probe amplification (MLPA1) were used to detect sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5% (n542 out of 290) in Chinese IPAH patients, and 53.3% (n58 out of 15) in HPAH patients. RGT mutation rate was 3.1% (n57 out of 229) and represented 14% (n57 out of 50) of all identified mutations. 25 BMPR2 mutations were newly identified.Patients in this study were younger than other reported PAH subjects. BMPR2 mutation carriers were ,6 yrs younger at diagnosis than noncarriers (p50.002), but this relationship was significant only in the female group, which was larger. The proportion of females carrying a BMPR2 mutation was half that of males (12.8% versus 25.3%; p50.008).Our results indicate that the overall genetics of Chinese PAH patients is similar to that of other populations, but the clinical picture differs by the precocity of the disease in the whole patient group, and the lower proportion of females found to carry a BMPR2 mutation.

BMPR2 Mutations Influence Phenotype More Obviously in Male Patients With Pulmonary Arterial Hypertension

“…6,14 Patients were screened for BMPR2 mutation by direct sequencing and large size rearrangements (RGTs) detection. 15 Direct screening using an ABI 3730 (Applied Biosystems, CA) was adopted to detect the point mutations in the coding regions and the intron/ exon boundaries of BMPR2. The BMPR2 gene was screened for RGTs using the SALSA MLPA P093 HHT probe mix kit (MRCHolland BV).…”

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Following the demonstration of 50 BMPR2 mutations, including 25 novel mutation sites, in 305 Chinese IPAH and HPAH patients, 15 we analyzed their phenotype-genotype relationship. The aim was to investigate the influence of BMPR2 mutations on the clinical trait and whether this influence is associated with sex.

Background-BMPR2 mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH).

The influence of BMPR2 mutations on clinical outcome is not concordant in different ethnic groups.

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“…Following the demonstration of 50 BMPR2 mutations, including 25 novel mutation sites, in 305 Chinese IPAH and HPAH patients, 15 we analyzed their phenotype-genotype relationship. The aim was to investigate the influence of BMPR2 mutations on the clinical trait and whether this influence is associated with sex.…”

Pulmonary arterial hypertension in familial hemiplegic migraine with ATP1A2 channelopathy

“…Involvement of mutations in genes encoding for members of the transforming growth factor-b signalling pathway (BMPR2, ACVRL1, ENG and SMAD8) has been demonstrated in the development of heritable PAH, allowing novel experimental and clinical approaches [2][3][4]. However, ,30% of familial forms of PAH remain without any identification of genetic mutations.…”

The study of risk in pulmonary arterial hypertension

“…Similarly, the French registry equation had good reproducibly when tested in a Chinese cohort [12] and the REVEAL cohort [13].…”