2022 Fiscal Year Final Research Report
Identification of novel causal genes in patients clinically diagnosed with Mowat-Wilson syndrome presenting Hirschsprung disease
| Project/Area Number |
19K09062
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Institute for Developmental Research Aichi Developmental Disability Center |
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Principal Investigator |
Yamada Kenichiro 愛知県医療療育総合センター発達障害研究所, 遺伝子医療研究部, 主任研究員 (30291173)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 精神運動発達遅滞 / 特徴的な顔貌 / モワット・ウィルソン症候群 / ZEB2 / TBX1 / DiGeorge症候群 |
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| Outline of Final Research Achievements |
Mowat-Wilson syndrome (MOWS) is a congenital disorder characterized by intellectual disability, epilepsy, microcephaly, characteristic facial features, and multiple congenital anomalies including Hirschsprung disease. MOWS is an autosomal dominant disorder caused by a loss-of-function mutation in the ZEB2 gene. We have already identified ZEB2 mutations in 113 (65.3%) among 173 patients. However, the finding that approximately one-third of the patients with suspected MOWS showed uncertain etiology prompted us to hypothesize that there may be another causative gene. Therefore, we applied genomic microarray and whole exome sequencing, and successfully identified a same mutation in the TBX1 gene in two cases. The G310S mutation had previously been reported as a causative mutation of DiGeorge syndrome (DGS). The current cases presented a different combination of clinical features from the previously reported cases, revealing the diversity of symptoms of this mutation.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、MOWSと診断される症例の中に、DiGeorge症候群の患者が含まれる可能性があることが明らかとなった。MOWSやDiGeorge症候群の患者には、主症状のほかに、合併する症状とその組み合わせに多様性があり、非典型例の診断には困難を要する。本研究で同定された２症例には、既報のTBX1ミスセンス変異症例では報告のない症状が見られたため、本変異による症状の多様性が明らかになるとともに、DiGeorge症候群の非典型例の臨床的な診断の難しさが明らかとなった。すなわち、多くの症状を合併する疾患では、未同定の非典型例がまだ残されている可能性が示唆された。
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