Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis
Abstract Background SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non‐coding elements (CNEs) represent one of the most frequent cause of SHOX‐haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1793 |
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| author | Antonella Fanelli Silvia Vannelli Deepak Babu Simona Mellone Alessia Cucci Alice Monzani Wael Al Essa Andrea Secco Antonia Follenzi Simonetta Bellone Flavia Prodam Mara Giordano |
| author_facet | Antonella Fanelli Silvia Vannelli Deepak Babu Simona Mellone Alessia Cucci Alice Monzani Wael Al Essa Andrea Secco Antonia Follenzi Simonetta Bellone Flavia Prodam Mara Giordano |
| author_sort | Antonella Fanelli |
| collection | DOAJ |
| description | Abstract Background SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non‐coding elements (CNEs) represent one of the most frequent cause of SHOX‐haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. Methods Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. Results Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX‐haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX‐haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. Conclusion Our results strengthen the hypothesis that alterations of yet unidentified cis‐regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX‐haploinsufficiency. |
| first_indexed | 2024-12-17T17:16:29Z |
| format | Article |
| id | doaj.art-0809b76504b14cf68a465c985fbba9f8 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-12-17T17:16:29Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-0809b76504b14cf68a465c985fbba9f82022-12-21T21:39:55ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-01-01101n/an/a10.1002/mgg3.1793Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosisAntonella Fanelli0Silvia Vannelli1Deepak Babu2Simona Mellone3Alessia Cucci4Alice Monzani5Wael Al Essa6Andrea Secco7Antonia Follenzi8Simonetta Bellone9Flavia Prodam10Mara Giordano11Dipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyEndocrinologia Pediatrica Dipartimento di Pediatria e Specialità Pediatriche Ospedale Regina Margherita Citta della Salute e della Scienza Torino ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyLaboratorio di Genetica S.C.D.U Biochimica Clinica Azienda Ospedaliera Universitaria "Maggiore della Carità" Novara ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyDivisione di Pediatria AOU "Maggiore della Carità" Novara ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalySC Pediatria e DEA Pediatrico Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo Alessandria ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyDipartimento di Scienze della Salute Università del Piemonte Orientale Novara ItalyAbstract Background SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non‐coding elements (CNEs) represent one of the most frequent cause of SHOX‐haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. Methods Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. Results Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX‐haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX‐haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. Conclusion Our results strengthen the hypothesis that alterations of yet unidentified cis‐regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX‐haploinsufficiency.https://doi.org/10.1002/mgg3.1793array CGHenhancersLWDshort statureSHOX |
| spellingShingle | Antonella Fanelli Silvia Vannelli Deepak Babu Simona Mellone Alessia Cucci Alice Monzani Wael Al Essa Andrea Secco Antonia Follenzi Simonetta Bellone Flavia Prodam Mara Giordano Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis Molecular Genetics & Genomic Medicine array CGH enhancers LWD short stature SHOX |
| title | Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis |
| title_full | Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis |
| title_fullStr | Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis |
| title_full_unstemmed | Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis |
| title_short | Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri‐Weill dyschondrosteosis |
| title_sort | copy number variations residing outside the shox enhancer region are involved in short stature and leri weill dyschondrosteosis |
| topic | array CGH enhancers LWD short stature SHOX |
| url | https://doi.org/10.1002/mgg3.1793 |
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