Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform
<h3>Purpose</h3><p dir="ltr">The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a...
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2024
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| _version_ | 1864513510197690368 |
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| author | Rafah Mackeh (14151225) |
| author2 | Yasmin El Bsat (19239436) Asha Elmi (9592371) Hani Bibawi (19239439) Mohammed Yousuf Karim (8602092) Amel Hassan (14151231) Bernice Lo (3441317) |
| author2_role | author author author author author author |
| author_facet | Rafah Mackeh (14151225) Yasmin El Bsat (19239436) Asha Elmi (9592371) Hani Bibawi (19239439) Mohammed Yousuf Karim (8602092) Amel Hassan (14151231) Bernice Lo (3441317) |
| author_role | author |
| dc.creator.none.fl_str_mv | Rafah Mackeh (14151225) Yasmin El Bsat (19239436) Asha Elmi (9592371) Hani Bibawi (19239439) Mohammed Yousuf Karim (8602092) Amel Hassan (14151231) Bernice Lo (3441317) |
| dc.date.none.fl_str_mv | 2024-04-08T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s10875-024-01688-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Novel_Synonymous_Variant_in_i_IL7R_i_Causes_Preferential_Expression_of_the_Soluble_Isoform/26392807 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Primary immunodeficiency (PID) Severe Combined Immunodeficiency (SCID) IL-7Rα deficiency IL-7Rα exon 6 Altered splicing Synonymous variant |
| dc.title.none.fl_str_mv | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Purpose</h3><p dir="ltr">The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a severe combined immunodeficiency (SCID), which is characterized by lymphopenia and a T<sup>−</sup>B<sup>+</sup>NK<sup>+</sup> phenotype. The objective here was to diagnose two siblings displaying the T<sup>−</sup>B<sup>+</sup>NK<sup>+</sup> SCID phenotype as initial clinical genetic testing did not detect any variants in known SCID genes.</p><h3>Methods</h3><p dir="ltr">Whole genome sequencing (WGS) was utilized to identify potential variants causing the SCID phenotype. Splicing prediction tools were employed to assess the deleterious impact of the mutation. Polymerase Chain Reaction (PCR), Sanger sequencing, flow cytometry, and ELISA were then used to validate the pathogenicity of the detected mutation.</p><h3>Results</h3><p dir="ltr">We discovered a novel homozygous synonymous mutation in the <i>IL7R</i> gene. Our functional studies indicate that this variant is pathogenic, causing exon 6, which encodes the transmembrane domain, to be preferentially spliced out.</p><h3>Conclusion</h3><p dir="ltr">In this study, we identified a novel rare synonymous mutation causing a loss of IL-7Rα expression at the cellular membrane. This case demonstrates the value of reanalyzing genetic data based on the clinical phenotype and highlights the significance of functional studies in determining the pathogenicity of genetic variants.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-024-01688-8" target="_blank">https://dx.doi.org/10.1007/s10875-024-01688-8</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_adadf87d52cc65855b9e1e7e5450ab02 |
| identifier_str_mv | 10.1007/s10875-024-01688-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26392807 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble IsoformRafah Mackeh (14151225)Yasmin El Bsat (19239436)Asha Elmi (9592371)Hani Bibawi (19239439)Mohammed Yousuf Karim (8602092)Amel Hassan (14151231)Bernice Lo (3441317)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesPrimary immunodeficiency (PID)Severe Combined Immunodeficiency (SCID)IL-7Rα deficiencyIL-7Rα exon 6Altered splicingSynonymous variant<h3>Purpose</h3><p dir="ltr">The interleukin-7 receptor (IL-7R) is primarily expressed on lymphoid cells and plays a crucial role in the development, proliferation, and survival of T cells. Autosomal recessive mutations that disrupt IL-7Rα chain expression give rise to a severe combined immunodeficiency (SCID), which is characterized by lymphopenia and a T<sup>−</sup>B<sup>+</sup>NK<sup>+</sup> phenotype. The objective here was to diagnose two siblings displaying the T<sup>−</sup>B<sup>+</sup>NK<sup>+</sup> SCID phenotype as initial clinical genetic testing did not detect any variants in known SCID genes.</p><h3>Methods</h3><p dir="ltr">Whole genome sequencing (WGS) was utilized to identify potential variants causing the SCID phenotype. Splicing prediction tools were employed to assess the deleterious impact of the mutation. Polymerase Chain Reaction (PCR), Sanger sequencing, flow cytometry, and ELISA were then used to validate the pathogenicity of the detected mutation.</p><h3>Results</h3><p dir="ltr">We discovered a novel homozygous synonymous mutation in the <i>IL7R</i> gene. Our functional studies indicate that this variant is pathogenic, causing exon 6, which encodes the transmembrane domain, to be preferentially spliced out.</p><h3>Conclusion</h3><p dir="ltr">In this study, we identified a novel rare synonymous mutation causing a loss of IL-7Rα expression at the cellular membrane. This case demonstrates the value of reanalyzing genetic data based on the clinical phenotype and highlights the significance of functional studies in determining the pathogenicity of genetic variants.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Clinical Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s10875-024-01688-8" target="_blank">https://dx.doi.org/10.1007/s10875-024-01688-8</a></p>2024-04-08T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s10875-024-01688-8https://figshare.com/articles/journal_contribution/Novel_Synonymous_Variant_in_i_IL7R_i_Causes_Preferential_Expression_of_the_Soluble_Isoform/26392807CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263928072024-04-08T03:00:00Z |
| spellingShingle | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform Rafah Mackeh (14151225) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Primary immunodeficiency (PID) Severe Combined Immunodeficiency (SCID) IL-7Rα deficiency IL-7Rα exon 6 Altered splicing Synonymous variant |
| status_str | publishedVersion |
| title | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| title_full | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| title_fullStr | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| title_full_unstemmed | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| title_short | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| title_sort | Novel Synonymous Variant in<i> IL7R</i> Causes Preferential Expression of the Soluble Isoform |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Primary immunodeficiency (PID) Severe Combined Immunodeficiency (SCID) IL-7Rα deficiency IL-7Rα exon 6 Altered splicing Synonymous variant |