Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder
<p dir="ltr">Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | , , , , , , , , , , , , |
| Published: |
2024
|
| Subjects: | |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1864513509347295232 |
|---|---|
| author | Rulan Shaath (17112852) |
| author2 | Aljazi Al-Maraghi (14056975) Haytham Ali (6896447) Jehan AlRayahi (17346976) Adam D. Kennedy (6677894) Karen L. DeBalsi (5698928) Sura Hussein (14152557) Najwa Elbashir (18288934) Sujitha S. Padmajeya (14152698) Sasirekha Palaniswamy (14152563) Sarah H. Elsea (6677915) Ammira A. Akil (19326085) Noha A. Yousri (1392577) Khalid A. Fakhro (3158862) |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Rulan Shaath (17112852) Aljazi Al-Maraghi (14056975) Haytham Ali (6896447) Jehan AlRayahi (17346976) Adam D. Kennedy (6677894) Karen L. DeBalsi (5698928) Sura Hussein (14152557) Najwa Elbashir (18288934) Sujitha S. Padmajeya (14152698) Sasirekha Palaniswamy (14152563) Sarah H. Elsea (6677915) Ammira A. Akil (19326085) Noha A. Yousri (1392577) Khalid A. Fakhro (3158862) |
| author_role | author |
| dc.creator.none.fl_str_mv | Rulan Shaath (17112852) Aljazi Al-Maraghi (14056975) Haytham Ali (6896447) Jehan AlRayahi (17346976) Adam D. Kennedy (6677894) Karen L. DeBalsi (5698928) Sura Hussein (14152557) Najwa Elbashir (18288934) Sujitha S. Padmajeya (14152698) Sasirekha Palaniswamy (14152563) Sarah H. Elsea (6677915) Ammira A. Akil (19326085) Noha A. Yousri (1392577) Khalid A. Fakhro (3158862) |
| dc.date.none.fl_str_mv | 2024-03-04T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/metabo14030152 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Integrating_Genome_Sequencing_and_Untargeted_Metabolomics_in_Monozygotic_Twins_with_a_Rare_Complex_Neurological_Disorder/26491195 |
| 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 Medical biochemistry and metabolomics Neurosciences multi-omics approaches untargeted metabolomics whole-genome sequencing rare complex disease |
| dc.title.none.fl_str_mv | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy–Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in <i>ADGRG1</i>(p.Arg565Trp) and a novel variant in <i>CNTNAP1</i>(p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without contractures, respectively. The twins exhibited symptoms that overlapped with both of these conditions. The results of the untargeted metabolomics analysis revealed significant metabolic perturbations relating to neurodevelopmental abnormalities, kidney dysfunction, and microbiome. The significant metabolites belong to essential pathways such as lipids and amino acid metabolism. The identification of variants in two genes, combined with the support of metabolic perturbation, demonstrates the rarity and complexity of this phenotype and provides valuable insights into its underlying mechanisms.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolites<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/10.3390/metabo14030152" target="_blank">https://dx.doi.org/10.3390/metabo14030152</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_a3f08b6a11d99f6fedbb59444ef79afd |
| identifier_str_mv | 10.3390/metabo14030152 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26491195 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological DisorderRulan Shaath (17112852)Aljazi Al-Maraghi (14056975)Haytham Ali (6896447)Jehan AlRayahi (17346976)Adam D. Kennedy (6677894)Karen L. DeBalsi (5698928)Sura Hussein (14152557)Najwa Elbashir (18288934)Sujitha S. Padmajeya (14152698)Sasirekha Palaniswamy (14152563)Sarah H. Elsea (6677915)Ammira A. Akil (19326085)Noha A. Yousri (1392577)Khalid A. Fakhro (3158862)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsNeurosciencesmulti-omics approachesuntargeted metabolomicswhole-genome sequencingrare complex disease<p dir="ltr">Multi-omics approaches, which integrate genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools in the diagnosis of rare diseases. We used untargeted metabolomics and whole-genome sequencing (WGS) to gain a more comprehensive understanding of a rare disease with a complex presentation affecting female twins from a consanguineous family. The sisters presented with polymicrogyria, a Dandy–Walker malformation, respiratory distress, and multiorgan dysfunctions. Through WGS, we identified two rare homozygous variants in both subjects, a pathogenic variant in <i>ADGRG1</i>(p.Arg565Trp) and a novel variant in <i>CNTNAP1</i>(p.Glu910Val). These genes have been previously associated with autosomal recessive polymicrogyria and hypomyelinating neuropathy with/without contractures, respectively. The twins exhibited symptoms that overlapped with both of these conditions. The results of the untargeted metabolomics analysis revealed significant metabolic perturbations relating to neurodevelopmental abnormalities, kidney dysfunction, and microbiome. The significant metabolites belong to essential pathways such as lipids and amino acid metabolism. The identification of variants in two genes, combined with the support of metabolic perturbation, demonstrates the rarity and complexity of this phenotype and provides valuable insights into its underlying mechanisms.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolites<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/10.3390/metabo14030152" target="_blank">https://dx.doi.org/10.3390/metabo14030152</a></p>2024-03-04T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/metabo14030152https://figshare.com/articles/journal_contribution/Integrating_Genome_Sequencing_and_Untargeted_Metabolomics_in_Monozygotic_Twins_with_a_Rare_Complex_Neurological_Disorder/26491195CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/264911952024-03-04T03:00:00Z |
| spellingShingle | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder Rulan Shaath (17112852) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Neurosciences multi-omics approaches untargeted metabolomics whole-genome sequencing rare complex disease |
| status_str | publishedVersion |
| title | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| title_full | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| title_fullStr | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| title_full_unstemmed | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| title_short | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| title_sort | Integrating Genome Sequencing and Untargeted Metabolomics in Monozygotic Twins with a Rare Complex Neurological Disorder |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Neurosciences multi-omics approaches untargeted metabolomics whole-genome sequencing rare complex disease |