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In recent investigations, the gene NAT10 (HGNC:29830) has been implicated in schizophrenia (MONDO_0005090) based on genetic screening in a nuclear family. The study identified multiple rare transmitted variants segregating with the disorder, emphasizing the potential role of chromatin modulation and related cellular pathways in schizophrenia (PMID:37763159). This report provides an initial look into how alterations in NAT10 could contribute to the complex genetic landscape of this psychiatric condition.
Evaluation of the clinical validity reveals that the evidence currently falls into a Limited category. Segregation analysis in a single nuclear family demonstrated that a specific NAT10 variant, c.2433G>T (p.Glu811Asp), co-segregates with the schizophrenia phenotype. Although the report identifies this variant alongside others in a polygenic framework, the limited number of unrelated probands and the absence of replicated segregation data in additional families necessitate cautious interpretation (PMID:37763159).
Genetic evidence for NAT10’s role in schizophrenia is based on the identification of the c.2433G>T (p.Glu811Asp) variant, which adheres to rigorous HGVS standards. The variant was observed to segregate with the disorder in the family studied, where multiple affected individuals carry this allele. This finding supports its consideration as a potential risk factor even though the evidence comes from a single family cohort. Additional variant classes and recurrence in other patients have not yet been documented, limiting the generalizability of the association (PMID:37763159).
The inheritance pattern suggested by the study is consistent with an autosomal dominant mode of transmission, as the variant appears to be heterozygous in affected individuals within the nuclear family. While the overall polygenic nature of schizophrenia is well recognized, in this instance the transmitted NAT10 variant may contribute to a dominant model of risk in the context of other co‐segregating genes. Segregation details indicate that additional affected relatives were present; however, quantitative segregation data remain limited, underscoring the need for further studies.
Functional evidence directly linking NAT10 to schizophrenia is currently absent from the available data. Although extensive functional studies on NAT10 exist in other disease contexts (such as cancer and progeria), none of these experiments address its role in the neuronal or psychiatric domain. The lack of mechanistic studies in schizophrenia leaves a gap in understanding how the c.2433G>T (p.Glu811Asp) variant specifically disrupts biological processes relevant to neural function and behavior (PMID:37763159).
In summary, while the segregation of a NAT10 variant with schizophrenia in a nuclear family provides an intriguing genetic lead, the overall evidence remains limited. Additional independent studies and functional validations will be essential to confirm NAT10 as a bona fide risk gene for schizophrenia and to elucidate its contribution to the disease mechanism. Key take‑home: Currently, NAT10 represents a promising candidate gene for schizophrenia with potential clinical utility in risk assessment, pending further corroborative evidence.
Gene–Disease AssociationLimitedSegregation data from a single nuclear family demonstrates co‐segregation of the NAT10 c.2433G>T (p.Glu811Asp) variant with schizophrenia (PMID:37763159), but independent replication is lacking. Genetic EvidenceLimitedOnly one rare coding variant in NAT10 has been identified in the context of schizophrenia in a single family, meeting strict HGVS standards but requiring further validation in larger cohorts (PMID:37763159). Functional EvidenceLimitedNo direct functional studies linking the NAT10 variant to schizophrenia pathogenesis have been reported, despite evidence from other disease areas. |