A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes
<p dir="ltr">Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further char...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2023
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| _version_ | 1864513508047060992 |
|---|---|
| author | Alya A. Al-Kurbi (18324927) |
| author2 | Elbay Aliyev (14056972) Sana AlSa’afin (19420597) Waleed Aamer (14056969) Sasirekha Palaniswamy (14152563) Aljazi Al-Maraghi (14056975) Houda Kilani (18543973) Ammira Al-Shabeeb Akil (15143925) Mitchell A. Stotland (15220174) Khalid A. Fakhro (3158862) |
| author2_role | author author author author author author author author author |
| author_facet | Alya A. Al-Kurbi (18324927) Elbay Aliyev (14056972) Sana AlSa’afin (19420597) Waleed Aamer (14056969) Sasirekha Palaniswamy (14152563) Aljazi Al-Maraghi (14056975) Houda Kilani (18543973) Ammira Al-Shabeeb Akil (15143925) Mitchell A. Stotland (15220174) Khalid A. Fakhro (3158862) |
| author_role | author |
| dc.creator.none.fl_str_mv | Alya A. Al-Kurbi (18324927) Elbay Aliyev (14056972) Sana AlSa’afin (19420597) Waleed Aamer (14056969) Sasirekha Palaniswamy (14152563) Aljazi Al-Maraghi (14056975) Houda Kilani (18543973) Ammira Al-Shabeeb Akil (15143925) Mitchell A. Stotland (15220174) Khalid A. Fakhro (3158862) |
| dc.date.none.fl_str_mv | 2023-03-31T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/genes14040849 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/A_Complex_Intrachromosomal_Rearrangement_Disrupting_i_IRF6_i_in_a_Family_with_Popliteal_Pterygium_and_Van_der_Woude_Syndromes/26661631 |
| 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 popliteal pterygium syndrome 1q32 IRF6 gene Cleft palate cleft lip syndactyly intrachromosomal rearrangements whole-genome sequencing |
| dc.title.none.fl_str_mv | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further characterized by having lower lip pits. Popliteal pterygium syndrome (PPS) is a more severe form of VWS, normally characterized by orofacial clefts, lower lip pits, skin webbing, skeletal anomalies and syndactyly of toes and fingers. Both syndromes are inherited in an autosomal dominant manner, usually caused by heterozygous mutations in the Interferon Regulatory Factor 6 (<i>IRF6</i>) gene. Here we report the case of a two-generation family where the index presented with popliteal pterygium syndrome while both the father and sister had clinical features of van der woude syndrome, but without any point mutations detected by re-sequencing of known gene panels or microarray testing. Using whole genome sequencing (WGS) followed by local de novo assembly, we discover and validate a copy-neutral, 429 kb complex intra-chromosomal rearrangement in the long arm of chromosome 1, disrupting the <i>IRF6</i> gene. This variant is copy-neutral, novel against publicly available databases, and segregates in the family in an autosomal dominant pattern. This finding suggests that missing heritability in rare diseases may be due to complex genomic rearrangements that can be resolved by WGS and de novo assembly, helping deliver answers to patients where no genetic etiology was identified by other means.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<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/genes14040849" target="_blank">https://dx.doi.org/10.3390/genes14040849</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e1087e1cd52a1b09347c61184e778721 |
| identifier_str_mv | 10.3390/genes14040849 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26661631 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude SyndromesAlya A. Al-Kurbi (18324927)Elbay Aliyev (14056972)Sana AlSa’afin (19420597)Waleed Aamer (14056969)Sasirekha Palaniswamy (14152563)Aljazi Al-Maraghi (14056975)Houda Kilani (18543973)Ammira Al-Shabeeb Akil (15143925)Mitchell A. Stotland (15220174)Khalid A. Fakhro (3158862)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencespopliteal pterygium syndrome1q32IRF6 geneCleft palatecleft lipsyndactylyintrachromosomal rearrangementswhole-genome sequencing<p dir="ltr">Clefts of the lip and/or palate (CL/P) are considered the most common form of congenital anomalies occurring either in isolation or in association with other clinical features. Van der woude syndrome (VWS) is associated with about 2% of all CL/P cases and is further characterized by having lower lip pits. Popliteal pterygium syndrome (PPS) is a more severe form of VWS, normally characterized by orofacial clefts, lower lip pits, skin webbing, skeletal anomalies and syndactyly of toes and fingers. Both syndromes are inherited in an autosomal dominant manner, usually caused by heterozygous mutations in the Interferon Regulatory Factor 6 (<i>IRF6</i>) gene. Here we report the case of a two-generation family where the index presented with popliteal pterygium syndrome while both the father and sister had clinical features of van der woude syndrome, but without any point mutations detected by re-sequencing of known gene panels or microarray testing. Using whole genome sequencing (WGS) followed by local de novo assembly, we discover and validate a copy-neutral, 429 kb complex intra-chromosomal rearrangement in the long arm of chromosome 1, disrupting the <i>IRF6</i> gene. This variant is copy-neutral, novel against publicly available databases, and segregates in the family in an autosomal dominant pattern. This finding suggests that missing heritability in rare diseases may be due to complex genomic rearrangements that can be resolved by WGS and de novo assembly, helping deliver answers to patients where no genetic etiology was identified by other means.</p><h2>Other Information</h2><p dir="ltr">Published in: Genes<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/genes14040849" target="_blank">https://dx.doi.org/10.3390/genes14040849</a></p>2023-03-31T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/genes14040849https://figshare.com/articles/journal_contribution/A_Complex_Intrachromosomal_Rearrangement_Disrupting_i_IRF6_i_in_a_Family_with_Popliteal_Pterygium_and_Van_der_Woude_Syndromes/26661631CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/266616312023-03-31T09:00:00Z |
| spellingShingle | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes Alya A. Al-Kurbi (18324927) Biological sciences Genetics Biomedical and clinical sciences Clinical sciences popliteal pterygium syndrome 1q32 IRF6 gene Cleft palate cleft lip syndactyly intrachromosomal rearrangements whole-genome sequencing |
| status_str | publishedVersion |
| title | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| title_full | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| title_fullStr | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| title_full_unstemmed | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| title_short | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| title_sort | A Complex Intrachromosomal Rearrangement Disrupting <i>IRF6 </i>in a Family with Popliteal Pterygium and Van der Woude Syndromes |
| topic | Biological sciences Genetics Biomedical and clinical sciences Clinical sciences popliteal pterygium syndrome 1q32 IRF6 gene Cleft palate cleft lip syndactyly intrachromosomal rearrangements whole-genome sequencing |