Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review
Background:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenita...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.853183/full |
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| author | Youqing Fu Wanfang Xu Qingming Wang Qingming Wang Yangyang Lin Peiqing He Peiqing He Yanhui Liu Yanhui Liu Haiming Yuan Haiming Yuan |
| author_facet | Youqing Fu Wanfang Xu Qingming Wang Qingming Wang Yangyang Lin Peiqing He Peiqing He Yanhui Liu Yanhui Liu Haiming Yuan Haiming Yuan |
| author_sort | Youqing Fu |
| collection | DOAJ |
| description | Background:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenital anomalies. Currently, more than 300 MWS patients have been described in the literature, and nearly 280 variants in ZEB2 have been identified.Methods: In this study, we report three unrelated Chinese patients presenting multiple congenital anomalies that were consistent with those of MWS. Whole-exome sequencing (WES) was used to identify the causative variants.Results: WES identified two novel de novo frameshift variants in ZEB2 (NM_014795.4:c.2136delC, p. Lys713Serfs*3 and c.2740delG, p. Gln914Argfs*16) in patients 1 and 2, respectively, and a novel de novo splicing variant in ZEB2 (NM_014795.4:c.808-2delA) in patient 3, all of which were confirmed by Sanger sequencing. Next, we systematically reviewed the clinical characteristics of Chinese and Caucasian MWS patients. We revealed a higher incidence of constipation in Chinese MWS patients compared to that previously reported in Caucasian cohorts, while the incidence of Hirschsprung disease and happy demeanor was lower in Chinese MWS patients and that epilepsy in Chinese MWS patients could be well-controlled compared to that in Caucasian MWS individuals.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical characteristics of MWS. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with MWS. |
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| language | English |
| last_indexed | 2024-12-12T09:34:52Z |
| publishDate | 2022-05-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-5ff2400927254d0dac5a95e63c16bc112022-12-22T00:28:44ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-05-011310.3389/fgene.2022.853183853183Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic ReviewYouqing Fu0Wanfang Xu1Qingming Wang2Qingming Wang3Yangyang Lin4Peiqing He5Peiqing He6Yanhui Liu7Yanhui Liu8Haiming Yuan9Haiming Yuan10Affiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaDongguan Institute of Reproductive and Genetic Research, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaDongguan Institute of Reproductive and Genetic Research, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaDongguan Institute of Reproductive and Genetic Research, Dongguan, ChinaAffiliated Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan, ChinaDongguan Institute of Reproductive and Genetic Research, Dongguan, ChinaBackground:ZEB2 gene mutations or deletions cause Mowat-Wilson syndrome (MWS), which is characterized by distinctive facial features, global developmental delay, intellectual disability, epilepsy, friendly and happy personalities, congenital heart disease, Hirschsprung disease and multiple congenital anomalies. Currently, more than 300 MWS patients have been described in the literature, and nearly 280 variants in ZEB2 have been identified.Methods: In this study, we report three unrelated Chinese patients presenting multiple congenital anomalies that were consistent with those of MWS. Whole-exome sequencing (WES) was used to identify the causative variants.Results: WES identified two novel de novo frameshift variants in ZEB2 (NM_014795.4:c.2136delC, p. Lys713Serfs*3 and c.2740delG, p. Gln914Argfs*16) in patients 1 and 2, respectively, and a novel de novo splicing variant in ZEB2 (NM_014795.4:c.808-2delA) in patient 3, all of which were confirmed by Sanger sequencing. Next, we systematically reviewed the clinical characteristics of Chinese and Caucasian MWS patients. We revealed a higher incidence of constipation in Chinese MWS patients compared to that previously reported in Caucasian cohorts, while the incidence of Hirschsprung disease and happy demeanor was lower in Chinese MWS patients and that epilepsy in Chinese MWS patients could be well-controlled compared to that in Caucasian MWS individuals.Conclusion: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical characteristics of MWS. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with MWS.https://www.frontiersin.org/articles/10.3389/fgene.2022.853183/fullMowat-Wilson syndromeZEB2epilepsyhirschsprung diseasehappy demeanor |
| spellingShingle | Youqing Fu Wanfang Xu Qingming Wang Qingming Wang Yangyang Lin Peiqing He Peiqing He Yanhui Liu Yanhui Liu Haiming Yuan Haiming Yuan Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review Frontiers in Genetics Mowat-Wilson syndrome ZEB2 epilepsy hirschsprung disease happy demeanor |
| title | Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review |
| title_full | Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review |
| title_fullStr | Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review |
| title_full_unstemmed | Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review |
| title_short | Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review |
| title_sort | three novel de novo zeb2 variants identified in three unrelated chinese patients with mowat wilson syndrome and a systematic review |
| topic | Mowat-Wilson syndrome ZEB2 epilepsy hirschsprung disease happy demeanor |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.853183/full |
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