An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

Navas Tejedor P; Tenorio Castaño J; Palomino Doza J; Arias Lajara P; Gordo Trujillo G; López Meseguer M; Román Broto A; Lapunzina Abadía P; Escribano Subía P

doi:10.1111/cge.12869

An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

Navas Tejedor P ^{1,

5},

Lapunzina Abadía P ²,

Escribano Subía P ⁵

Affiliations

1. Servicio de Cardiología, Hospital Universitario Gregorio Marañón, Madrid, Spain.
Authors
Navas Tejedor P^{1,

5}
(1 author)
2. CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
Authors
Tenorio Castaño J²
Arias Lajara P²
Gordo Trujillo G²
Lapunzina Abadía P²
(4 authors)
3. Unidad de Cardiopatías Familiares. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain.
Authors
Palomino Doza J³
(1 author)
4. Servicio de Neumología, Hospital Universitario Vall d'Hebrón, Barcelona, Spain.
Authors
López Meseguer M⁴
Román Broto A⁴
(2 authors)
5. Red de Investigación Cardiovascular (RIC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Authors
Navas Tejedor P^{1,

5}
Escribano Subía P⁵
(2 authors)

ORCIDs linked to this article

Clinical Genetics, 04 Nov 2016, 91(3):453-457
https://doi.org/10.1111/cge.12869 PMID: 27649371

Abstract

Pulmonary arterial hypertension (PAH) is a rare devastating disease characterized by a high genetic heterogeneity with several related genes recently described, including BMPR2,TBX4 and KCNK3. The association between KCNK3 and PAH has been recently identified, but the prognosis and phenotype associated with these mutations have been poorly described. We studied a series of 136 idiopathic and hereditary PAH Spanish patients for BMPR2, TBX4 and KCNK3 mutations. We report the results of KCNK3 in which we were able to describe two new mutations (p.Gly106Arg and p.Leu214Arg) in three patients. The first one was found in a patient belonging to a consanguineous Romani family, who carried a homozygous mutation in KCNK3 and developed a severe and early form of the disease. To the best of our knowledge, this is the first time that a homozygous mutation in KCNK3 is reported in a PAH patient. The second one was found in a patient who presented at the young adult age a severe form of the disease. The present report supports the contribution of KCNK3 mutations to the genetic etiology of PAH and strongly suggests that mutations in KCNK3 follow incomplete dominance with worsening of the clinical features in homozygous patients.

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An homozygous mutation in KCNK3 is associated with an aggressive form of hereditary pulmonary arterial hypertension.

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