Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing
<p dir="ltr">This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autoso...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , , |
| منشور في: |
2023
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| _version_ | 1864513507582541824 |
|---|---|
| author | Vijay Gupta (209146) |
| author2 | Afif Ben-Mahmoud (13913550) Bonsu Ku (85687) Dinesh Velayutham (5444072) Zainab Jan (17306614) Abdi Yousef Aden (19459540) Ahmad Kubbar (17306620) Fouad Alshaban (6176771) Lawrence W. Stanton (6707191) Puthen Veettil Jithesh (12040358) Lawrence C. Layman (13913559) Hyung-Goo Kim (728597) |
| author2_role | author author author author author author author author author author author |
| author_facet | Vijay Gupta (209146) Afif Ben-Mahmoud (13913550) Bonsu Ku (85687) Dinesh Velayutham (5444072) Zainab Jan (17306614) Abdi Yousef Aden (19459540) Ahmad Kubbar (17306620) Fouad Alshaban (6176771) Lawrence W. Stanton (6707191) Puthen Veettil Jithesh (12040358) Lawrence C. Layman (13913559) Hyung-Goo Kim (728597) |
| author_role | author |
| dc.creator.none.fl_str_mv | Vijay Gupta (209146) Afif Ben-Mahmoud (13913550) Bonsu Ku (85687) Dinesh Velayutham (5444072) Zainab Jan (17306614) Abdi Yousef Aden (19459540) Ahmad Kubbar (17306620) Fouad Alshaban (6176771) Lawrence W. Stanton (6707191) Puthen Veettil Jithesh (12040358) Lawrence C. Layman (13913559) Hyung-Goo Kim (728597) |
| dc.date.none.fl_str_mv | 2023-10-31T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fpsyt.2023.1251884 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Identification_of_two_novel_autism_genes_i_TRPC4_i_and_i_SCFD2_i_in_Qatar_simplex_families_through_exome_sequencing/26798140 |
| 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 Neurosciences exome sequencing autism intellectual disability digenic TRPC4 SCFD2 |
| dc.title.none.fl_str_mv | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of de novo and homozygous missense and splice variants. Multiple individuals displayed more than one candidate variant, suggesting the potential involvement of digenic or oligogenic models. These variants were absent in the Genome Aggregation Database (gnomAD) and exhibited extremely low frequencies in the local control population dataset. Two novel autism genes, <i>TRPC4 </i>and <i>SCFD2</i>, were discovered in two Qatari autism individuals. Furthermore, the <i>D651A</i> substitution in<i> CLCN3</i> and the splice acceptor variant in <i>DHX30</i> were identified as likely deleterious mutations. Protein modeling was utilized to evaluate the potential impact of three missense variants in <i>DEAF1, CLCN3, </i>and <i>SCFD2</i> on their respective structures and functions, which strongly supported the pathogenic natures of these variants. The presence of multiple <i>de novo</i> mutations across trios underscored the significant contribution of de novo mutations to the genetic etiology of ASD. Functional assays and further investigations are necessary to confirm the pathogenicity of the identified genes and determine their significance in ASD. Overall, this study sheds light on the genetic factors underlying ASD in Qatar and highlights the importance of considering diverse populations in ASD research.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Psychiatry<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/10.3389/fpsyt.2023.1251884" target="_blank">https://dx.doi.org/10.3389/fpsyt.2023.1251884</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_52f25751f697a3b6bdc354333193b1a8 |
| identifier_str_mv | 10.3389/fpsyt.2023.1251884 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26798140 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencingVijay Gupta (209146)Afif Ben-Mahmoud (13913550)Bonsu Ku (85687)Dinesh Velayutham (5444072)Zainab Jan (17306614)Abdi Yousef Aden (19459540)Ahmad Kubbar (17306620)Fouad Alshaban (6176771)Lawrence W. Stanton (6707191)Puthen Veettil Jithesh (12040358)Lawrence C. Layman (13913559)Hyung-Goo Kim (728597)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesNeurosciencesexome sequencingautismintellectual disabilitydigenicTRPC4SCFD2<p dir="ltr">This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of de novo and homozygous missense and splice variants. Multiple individuals displayed more than one candidate variant, suggesting the potential involvement of digenic or oligogenic models. These variants were absent in the Genome Aggregation Database (gnomAD) and exhibited extremely low frequencies in the local control population dataset. Two novel autism genes, <i>TRPC4 </i>and <i>SCFD2</i>, were discovered in two Qatari autism individuals. Furthermore, the <i>D651A</i> substitution in<i> CLCN3</i> and the splice acceptor variant in <i>DHX30</i> were identified as likely deleterious mutations. Protein modeling was utilized to evaluate the potential impact of three missense variants in <i>DEAF1, CLCN3, </i>and <i>SCFD2</i> on their respective structures and functions, which strongly supported the pathogenic natures of these variants. The presence of multiple <i>de novo</i> mutations across trios underscored the significant contribution of de novo mutations to the genetic etiology of ASD. Functional assays and further investigations are necessary to confirm the pathogenicity of the identified genes and determine their significance in ASD. Overall, this study sheds light on the genetic factors underlying ASD in Qatar and highlights the importance of considering diverse populations in ASD research.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Psychiatry<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/10.3389/fpsyt.2023.1251884" target="_blank">https://dx.doi.org/10.3389/fpsyt.2023.1251884</a></p>2023-10-31T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fpsyt.2023.1251884https://figshare.com/articles/journal_contribution/Identification_of_two_novel_autism_genes_i_TRPC4_i_and_i_SCFD2_i_in_Qatar_simplex_families_through_exome_sequencing/26798140CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/267981402023-10-31T06:00:00Z |
| spellingShingle | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing Vijay Gupta (209146) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences exome sequencing autism intellectual disability digenic TRPC4 SCFD2 |
| status_str | publishedVersion |
| title | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| title_full | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| title_fullStr | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| title_full_unstemmed | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| title_short | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| title_sort | Identification of two novel autism genes, <i>TRPC4</i> and <i>SCFD2</i>, in Qatar simplex families through exome sequencing |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Neurosciences exome sequencing autism intellectual disability digenic TRPC4 SCFD2 |