FAM174B – Schizophrenia

This summary evaluates the association between FAM174B (HGNC:34339) and schizophrenia (MONDO:0005090) based on evidence derived from candidate gene studies using whole‐exome sequencing. Two independent families were examined, and indels in FAM174B were detected in affected siblings, suggesting a potential link with the schizophrenia phenotype (PMID:30226068). Although the sample size is small, the familial clustering provides initial support for the association, albeit with limited statistical power.

Genetic evidence stems from the observation that in one family two siblings and in a second family another two siblings were diagnosed with schizophrenia, consistent with an autosomal recessive inheritance pattern. The segregation analysis shows that affected siblings carry candidate indels in FAM174B, with each family contributing additional affected individuals beyond the index case. However, the overall number of probands is modest (four affected individuals in total), which restricts the strength of the genetic evidence.

A detailed assessment of variant data reveals that while indels were reported across several genes in the study, no specific HGVS‐compliant variant has been unambiguously attributed to FAM174B. In accordance with the evaluation criteria, no variant string meeting the required format (beginning with “c.” and ending with “)” with a single space before “(p…”) could be extracted for FAM174B. As such, the genetic evidence is derived from segregation analysis and candidate identification rather than from a clearly defined pathogenic variant.

Functional evidence directly linking FAM174B to schizophrenia is currently lacking. Although FAM174B is mentioned in other experimental studies in different disease contexts, the functional studies provided in the supplied evidence focus on cerebellar ataxia rather than schizophrenia. Thus, no experimental assays, expression analyses, or animal models have conclusively demonstrated a pathogenic mechanism for FAM174B in schizophrenia. This absence of direct functional support further limits the overall evaluation of the association.

In integrating the genetic and experimental findings, the available data supports a limited association between FAM174B and schizophrenia. The candidate gene approach identified indels in two families with multiple affected siblings, which is consistent with an autosomal recessive mode of inheritance; however, the small number of probands and the lack of corroborating functional studies caution against a definitive interpretation. Additional studies with larger cohorts and direct functional assays are required to clarify the pathogenic role of FAM174B in schizophrenia.

Key take‑home message: While preliminary familial evidence implicates FAM174B in schizophrenia, further extensive genetic and functional investigations are needed to establish its clinical utility in diagnosis.

References

• Bratislavske lekarske listy • 2018 • Determination of candidate genes involved in schizophrenia using the whole-exome sequencing PMID:30226068

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