Expresividad variable de una mutación fundadora en el gen  EIF2AK4  en pacientes con enfermedad venooclusiva pulmonar hereditaria. Impacto en la supervivencia

Tejedor, Paula; Doza, Julián Palomino; Castaño, Jair Antonio Tenorio; Valls, Ana Belén Enguita; Reguero, J.J.R.; Meñaca, Amaya Martínez; González, Ignacio Hernández; Bueno, Héctor; Lapunzina, Pablo; Subías, Pilar Escribano

doi:10.1016/j.recesp.2017.03.030

Cited by 18 publications

(2 citation statements)

References 17 publications

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“…Finally, additional variants in genes with no documented implication in PCH/PVOD could also account for this discrepancy. Clinical follow up is needed for the individual at risk as the phenotype expression could appear later, as was the case in the founder EIF2AK4 mutation in the Iberian Romani population [11].…”

Section: Discussionmentioning

confidence: 99%

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Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension

Hassan¹,

Haidar²,

Arabi³

et al. 2019

BMC Med Genet

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BackgroundPulmonary hypertension (PH) remains one of the rarest and deadliest diseases. Pulmonary Capillary Hemangiomatosis (PCH) is one of the sub-classes of PH. It was identified using histological and molecular tools and is characterized by the proliferation of capillaries into the alveolar septae. Mutations in the gene encoding the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) have recently been linked to this particular subgroup of PH.MethodsIn our effort to unveil the genetic basis of idiopathic and familial cases of PH in Lebanon, we have used whole exome sequencing to document known and/or novel mutations in genes that could explain the underlying phenotype.ResultsWe showed bi-allelic mutations in EIF2AK4 in two non-consanguineous families: a novel non-sense mutation c.1672C > T (p.Q558*) and a previously documented deletion c.560_564drlAAGAA (p.K187Rfs9*). Our histological analysis coupled with the CT-scan results showed that the two patients with the p.Q558* mutation have PH. In contrast, only one of the individuals harboring the p.K187Rfs9* variant has a documented PCH while his older brother remains asymtomatic. Differential analysis of the variants in the genes of the neighboring network of EIF2AK4 between the two siblings identified a couple of interesting missense mutations that could account for this discrepancy.ConclusionThese findings represent a novel documentation of the involvement of EIF2AK4 in the different aspects of pulmonary hypertension. The absence of a molecular mechanism that relates the abrogated function of the protein to the phenotype is still a major hurdle in our understanding of the disease.

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Section: Discussionmentioning

confidence: 99%

“…These mutations were first found in an autosomal recessively inherited PCH familial case and in 20% of sporadic cases [10]. EIF2AK4 mutations are also found in PVOD patients, reinforcing the link of these two diseases to a common genetic risk factor [11–13].…”

Section: Introductionmentioning

confidence: 99%