TY - JOUR
T1 - Genetic evaluation in a cohort of 126 dutch pulmonary arterial hypertension patients
AU - van den Heuvel, Lieke M.
AU - Jansen, Samara M. A.
AU - Alsters, Suzanne I. M.
AU - Post, Marco C.
AU - van der Smagt, Jasper J.
AU - Handoko-de Man, Frances S.
AU - Peter van Tintelen, J.
AU - Gille, Hans
AU - Christiaans, Imke
AU - Noordegraaf, Anton Vonk
AU - Bogaard, Harmjan
AU - Houweling, Arjan C.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH.
AB - Pulmonary arterial hypertension (PAH) is a severe, life-threatening disease, and in some cases is caused by genetic defects. This study sought to assess the diagnostic yield of genetic testing in a Dutch cohort of 126 PAH patients. Historically, genetic testing in the Netherlands consisted of the analysis of BMPR2 and SMAD9. These genes were analyzed in 70 of the 126 patients. A (likely) pathogenic (LP/P) variant was detected in 22 (31%) of them. After the identification of additional PAH associated genes, a next generation sequencing (NGS) panel consisting of 19 genes was developed in 2018. Additional genetic testing was offered to the 48 BMPR2 and SMAD9 negative patients, out of which 28 opted for NGS analysis. In addition, this gene panel was analyzed in 56 newly identified idiopathic (IPAH) or pulmonary veno occlusive disease (PVOD) patients. In these 84 patients, NGS panel testing revealed LP/P variants in BMPR2 (N = 4), GDF2 (N = 2), EIF2AK4 (N = 1), and TBX4 (N = 3). Furthermore, 134 relatives of 32 probands with a LP/P variant were tested, yielding 41 carriers. NGS panel screening offered to IPAH/PVOD patients led to the identification of LP/P variants in GDF2, EIF2AK4, and TBX4 in six additional patients. The identification of LP/P variants in patients allows for screening of at-risk relatives, enabling the early identification of PAH.
KW - BMPR2
KW - EIF2AK4
KW - GDF2
KW - Genetic analysis
KW - NGS gene panel
KW - Pulmonary arterial hypertension
KW - TBX4
UR - http://www.scopus.com/inward/record.url?scp=85092475983&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/genes11101191
DO - https://doi.org/10.3390/genes11101191
M3 - Article
C2 - 33066286
SN - 2073-4425
VL - 11
SP - 1
EP - 12
JO - Genes
JF - Genes
IS - 10
M1 - 1191
ER -