Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension
<h3>Background</h3><p dir="ltr">Pulmonary 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 pr...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| مؤلفون آخرون: | , , , , , |
| منشور في: |
2019
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1864513513962078208 |
|---|---|
| author | Ossama K. Abou Hassan (18618628) |
| author2 | Wiam Haidar (5314565) Mariam Arabi (6339860) Hadi Skouri (5314571) Fadi Bitar (295982) Georges Nemer (295984) Imad Bou Akl (5059469) |
| author2_role | author author author author author author |
| author_facet | Ossama K. Abou Hassan (18618628) Wiam Haidar (5314565) Mariam Arabi (6339860) Hadi Skouri (5314571) Fadi Bitar (295982) Georges Nemer (295984) Imad Bou Akl (5059469) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ossama K. Abou Hassan (18618628) Wiam Haidar (5314565) Mariam Arabi (6339860) Hadi Skouri (5314571) Fadi Bitar (295982) Georges Nemer (295984) Imad Bou Akl (5059469) |
| dc.date.none.fl_str_mv | 2019-11-11T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12881-019-0915-7 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Novel_EIF2AK4_mutations_in_histologically_proven_pulmonary_capillary_hemangiomatosis_and_hereditary_pulmonary_arterial_hypertension/25907554 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Pulmonary hypertension EIF2AK4 Hemangiomatosis Exome Sequencing |
| dc.title.none.fl_str_mv | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Background</h3><p dir="ltr">Pulmonary 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.</p><h3>Methods</h3><p dir="ltr">In 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.</p><h3>Results</h3><p dir="ltr">We 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.</p><h3>Conclusion</h3><p dir="ltr">These 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.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12881-019-0915-7" target="_blank">https://dx.doi.org/10.1186/s12881-019-0915-7</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_bd296b8739bf33ffc5c7af11cd6a0bbe |
| identifier_str_mv | 10.1186/s12881-019-0915-7 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25907554 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertensionOssama K. Abou Hassan (18618628)Wiam Haidar (5314565)Mariam Arabi (6339860)Hadi Skouri (5314571)Fadi Bitar (295982)Georges Nemer (295984)Imad Bou Akl (5059469)Biomedical and clinical sciencesClinical sciencesPulmonary hypertensionEIF2AK4HemangiomatosisExomeSequencing<h3>Background</h3><p dir="ltr">Pulmonary 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.</p><h3>Methods</h3><p dir="ltr">In 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.</p><h3>Results</h3><p dir="ltr">We 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.</p><h3>Conclusion</h3><p dir="ltr">These 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.</p><h2>Other Information</h2><p dir="ltr">Published in: BMC Medical Genetics<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12881-019-0915-7" target="_blank">https://dx.doi.org/10.1186/s12881-019-0915-7</a></p>2019-11-11T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12881-019-0915-7https://figshare.com/articles/journal_contribution/Novel_EIF2AK4_mutations_in_histologically_proven_pulmonary_capillary_hemangiomatosis_and_hereditary_pulmonary_arterial_hypertension/25907554CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259075542019-11-11T03:00:00Z |
| spellingShingle | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension Ossama K. Abou Hassan (18618628) Biomedical and clinical sciences Clinical sciences Pulmonary hypertension EIF2AK4 Hemangiomatosis Exome Sequencing |
| status_str | publishedVersion |
| title | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| title_full | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| title_fullStr | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| title_full_unstemmed | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| title_short | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| title_sort | Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension |
| topic | Biomedical and clinical sciences Clinical sciences Pulmonary hypertension EIF2AK4 Hemangiomatosis Exome Sequencing |