8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects
Abstract Background 8q21.11 microdeletion syndrome is a rare chromosomal disorder characterized by recurrent dysmorphic features, a variable degree of intellectual disability and ocular, cardiac and hand/feet abnormalities. To date, ZFHX4 is the only candidate gene implicated in the ocular findings....
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Wiley
2021
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oai:doaj.org-article:a21fb15130e34021bb3464c79a22b09f2021-11-21T19:38:53Z8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects2324-926910.1002/mgg3.1811https://doaj.org/article/a21fb15130e34021bb3464c79a22b09f2021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1811https://doaj.org/toc/2324-9269Abstract Background 8q21.11 microdeletion syndrome is a rare chromosomal disorder characterized by recurrent dysmorphic features, a variable degree of intellectual disability and ocular, cardiac and hand/feet abnormalities. To date, ZFHX4 is the only candidate gene implicated in the ocular findings. In this study, we evaluated a patient with a de novo 8q21.13–21.3 deletion to define a new small region of overlap (SRO) for this entity. Methods We conducted a clinical evaluation and comparative genomic hybridization (CGH) 4x44K microarrays in a patient with de novo unbalanced translocation t(8;16)(q21; q11.2). Results The case, a 6‐year‐old boy, presented dysmorphic features including an elongated face, brachycephaly with a high forehead, an underdeveloped ala, thin upper lip, micrognathia, low‐set ears, hypotonia, mild intellectual disability, cortical atrophy with thin corpus callosum defect, and an atrial septal defect. No ocular abnormalities were found. Microarray analysis revealed a 9.6 Mb interstitial 8q21.11–21.3 deletion, not including the ZFHX4 gene. This microdeletion was confirmed in our patient through qPCR analysis, and both parents had a normal profile. Alignment analysis of our case defined a new SRO encompassing five genes. Among them, the HEY1 gene is involved in the embryonic development of the heart, central nervous system, and vascular system. Hrt1/Hey1 null mice show perinatal lethality due to congenital malformations of the aortic arch and its branch arteries. HEY1 has also been linked to the maintenance of neural stem cells, inhibition of oligodendrocyte differentiation, and myelin gene expression. Conclusion HEY1 is a candidate gene for both neurological and cardiac features of the 8q21.11 microdeletion syndrome and might, therefore, explain specific components of its pathophysiology.Ikhlas Ben AyedAmal BouzidFatma KammounAmal souissiOlfa JallouliSalma MallouliSouhir GuidaraSalma LoukilHajer AloulouFida JbeliSahar AouichaouiDorra AbidFatma AbdelhediChahnez TrikiHassen KamounSaber MasmoudiWileyarticle8q21.11 microdeletion syndromecardiac defectcomparative genomic hybridizationHEY1intellectual disabilityGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021) |
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8q21.11 microdeletion syndrome cardiac defect comparative genomic hybridization HEY1 intellectual disability Genetics QH426-470 |
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8q21.11 microdeletion syndrome cardiac defect comparative genomic hybridization HEY1 intellectual disability Genetics QH426-470 Ikhlas Ben Ayed Amal Bouzid Fatma Kammoun Amal souissi Olfa Jallouli Salma Mallouli Souhir Guidara Salma Loukil Hajer Aloulou Fida Jbeli Sahar Aouichaoui Dorra Abid Fatma Abdelhedi Chahnez Triki Hassen Kamoun Saber Masmoudi 8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| description |
Abstract Background 8q21.11 microdeletion syndrome is a rare chromosomal disorder characterized by recurrent dysmorphic features, a variable degree of intellectual disability and ocular, cardiac and hand/feet abnormalities. To date, ZFHX4 is the only candidate gene implicated in the ocular findings. In this study, we evaluated a patient with a de novo 8q21.13–21.3 deletion to define a new small region of overlap (SRO) for this entity. Methods We conducted a clinical evaluation and comparative genomic hybridization (CGH) 4x44K microarrays in a patient with de novo unbalanced translocation t(8;16)(q21; q11.2). Results The case, a 6‐year‐old boy, presented dysmorphic features including an elongated face, brachycephaly with a high forehead, an underdeveloped ala, thin upper lip, micrognathia, low‐set ears, hypotonia, mild intellectual disability, cortical atrophy with thin corpus callosum defect, and an atrial septal defect. No ocular abnormalities were found. Microarray analysis revealed a 9.6 Mb interstitial 8q21.11–21.3 deletion, not including the ZFHX4 gene. This microdeletion was confirmed in our patient through qPCR analysis, and both parents had a normal profile. Alignment analysis of our case defined a new SRO encompassing five genes. Among them, the HEY1 gene is involved in the embryonic development of the heart, central nervous system, and vascular system. Hrt1/Hey1 null mice show perinatal lethality due to congenital malformations of the aortic arch and its branch arteries. HEY1 has also been linked to the maintenance of neural stem cells, inhibition of oligodendrocyte differentiation, and myelin gene expression. Conclusion HEY1 is a candidate gene for both neurological and cardiac features of the 8q21.11 microdeletion syndrome and might, therefore, explain specific components of its pathophysiology. |
| format |
article |
| author |
Ikhlas Ben Ayed Amal Bouzid Fatma Kammoun Amal souissi Olfa Jallouli Salma Mallouli Souhir Guidara Salma Loukil Hajer Aloulou Fida Jbeli Sahar Aouichaoui Dorra Abid Fatma Abdelhedi Chahnez Triki Hassen Kamoun Saber Masmoudi |
| author_facet |
Ikhlas Ben Ayed Amal Bouzid Fatma Kammoun Amal souissi Olfa Jallouli Salma Mallouli Souhir Guidara Salma Loukil Hajer Aloulou Fida Jbeli Sahar Aouichaoui Dorra Abid Fatma Abdelhedi Chahnez Triki Hassen Kamoun Saber Masmoudi |
| author_sort |
Ikhlas Ben Ayed |
| title |
8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| title_short |
8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| title_full |
8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| title_fullStr |
8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| title_full_unstemmed |
8q21.11 microdeletion syndrome: Delineation of HEY1 as a candidate gene in neurodevelopmental and cardiac defects |
| title_sort |
8q21.11 microdeletion syndrome: delineation of hey1 as a candidate gene in neurodevelopmental and cardiac defects |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/a21fb15130e34021bb3464c79a22b09f |
| work_keys_str_mv |
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