Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects
Abstract We report a case of a 61‐year‐old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole‐genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment‐resistant schizophrenia (SCZ),...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Neuropsychopharmacology Reports |
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| Online Access: | https://doi.org/10.1002/npr2.12477 |
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| author | Sawako Furukawa Shusei Arafuka Hidekazu Kato Tomoo Ogi Norio Ozaki Masashi Ikeda Itaru Kushima |
| author_facet | Sawako Furukawa Shusei Arafuka Hidekazu Kato Tomoo Ogi Norio Ozaki Masashi Ikeda Itaru Kushima |
| author_sort | Sawako Furukawa |
| collection | DOAJ |
| description | Abstract We report a case of a 61‐year‐old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole‐genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment‐resistant schizophrenia (SCZ), and multiple congenital anomalies. Despite aggressive pharmacotherapy, she experienced persistent auditory hallucinations and negative symptoms. WGS revealed a 3 Mb deletion at 22q11.2 and a nonsense variant in MAP1A (c.4652T>G, p.Leu1551*). MAP1A, encoding microtubule‐associated protein 1A, is crucial for axon and dendrite development and has been implicated in autism spectrum disorder and SCZ. The MAP1A variant may contribute to the severe psychiatric phenotype, as it is thought to influence synaptic plasticity, a process also affected by 22q11.2 deletion. This case highlights the importance of WGS in identifying additional pathogenic variants that may explain phenotypic variability in 22q11.2DS. Thus, WGS can lead to a better understanding of the genetic architecture of 22q11.2DS. However, further studies are needed to elucidate the role of secondary genetic contributors in the diverse clinical presentations of 22q11.2DS. |
| format | Article |
| id | doaj-art-532c69a43b0c45068c05cf77d6eb5bfa |
| institution | OA Journals |
| issn | 2574-173X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neuropsychopharmacology Reports |
| spelling | doaj-art-532c69a43b0c45068c05cf77d6eb5bfa2025-08-20T01:57:27ZengWileyNeuropsychopharmacology Reports2574-173X2024-12-0144484785110.1002/npr2.12477Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defectsSawako Furukawa0Shusei Arafuka1Hidekazu Kato2Tomoo Ogi3Norio Ozaki4Masashi Ikeda5Itaru Kushima6Department of Psychiatry Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Psychiatry Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Psychiatry Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Genetics Research Institute of Environmental Medicine (RIeM), Nagoya University Nagoya JapanPathophysiology of Mental Disorders Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Psychiatry Nagoya University Graduate School of Medicine Nagoya JapanDepartment of Psychiatry Nagoya University Graduate School of Medicine Nagoya JapanAbstract We report a case of a 61‐year‐old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole‐genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment‐resistant schizophrenia (SCZ), and multiple congenital anomalies. Despite aggressive pharmacotherapy, she experienced persistent auditory hallucinations and negative symptoms. WGS revealed a 3 Mb deletion at 22q11.2 and a nonsense variant in MAP1A (c.4652T>G, p.Leu1551*). MAP1A, encoding microtubule‐associated protein 1A, is crucial for axon and dendrite development and has been implicated in autism spectrum disorder and SCZ. The MAP1A variant may contribute to the severe psychiatric phenotype, as it is thought to influence synaptic plasticity, a process also affected by 22q11.2 deletion. This case highlights the importance of WGS in identifying additional pathogenic variants that may explain phenotypic variability in 22q11.2DS. Thus, WGS can lead to a better understanding of the genetic architecture of 22q11.2DS. However, further studies are needed to elucidate the role of secondary genetic contributors in the diverse clinical presentations of 22q11.2DS.https://doi.org/10.1002/npr2.1247722q11.2 deletion syndromegenetics: Humanschizophrenia: Clinicaltreatment‐resistant schizophreniawhole‐genome sequencing |
| spellingShingle | Sawako Furukawa Shusei Arafuka Hidekazu Kato Tomoo Ogi Norio Ozaki Masashi Ikeda Itaru Kushima Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects Neuropsychopharmacology Reports 22q11.2 deletion syndrome genetics: Human schizophrenia: Clinical treatment‐resistant schizophrenia whole‐genome sequencing |
| title | Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects |
| title_full | Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects |
| title_fullStr | Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects |
| title_full_unstemmed | Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects |
| title_short | Treatment‐resistant schizophrenia with 22q11.2 deletion and additional genetic defects |
| title_sort | treatment resistant schizophrenia with 22q11 2 deletion and additional genetic defects |
| topic | 22q11.2 deletion syndrome genetics: Human schizophrenia: Clinical treatment‐resistant schizophrenia whole‐genome sequencing |
| url | https://doi.org/10.1002/npr2.12477 |
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