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This summary describes the evidence supporting a potential association between PABPC5 (HGNC:13629) and Tourette syndrome (MONDO_0007661). A microduplication event involving the Xq21.31 region, which spans PABPC5 along with another gene (PCDH11X), was identified in a family where Tourette syndrome co‐occurred with additional neuropsychiatric features. In this report, the male proband along with two affected brothers exhibited the duplication while an unaffected brother did not, suggesting a pattern consistent with an X‑linked mode of inheritance (PMID:23894120).
Genetic evidence is based on a single family study. The Xq21.31 microduplication was found in three brothers with Tourette syndrome, ADHD, and obsessive compulsive disorder, and its segregation with the phenotype in this family provides initial support for a contributory role of PABPC5 dosage alterations. However, because the evidence is derived from a limited case series and from a single extended family, the overall genetic support remains preliminary (PMID:23894120).
There is no independent replication of this finding, and no additional probands have been reported so far to expand the genetic evidence. The available evidence represents a structural (copy number) alteration rather than a sequence-level variant, and no HGVS-compliant coding change (starting with a c. and including a p. designation with three-letter amino acid codes) is provided for PABPC5. Consequently, the reported variant list for PABPC5 is currently empty.
Functional or experimental data supporting a mechanistic link between altered PABPC5 dosage and Tourette syndrome pathogenesis are lacking. No functional assays, animal models, or expression studies were reported that evaluate the impact of the Xq21.31 microduplication on gene function, leaving the pathogenic mechanism unresolved. This absence of experimental evidence limits our understanding of how the duplication might contribute to disease.
In integrating the genetic and functional findings, it is evident that while there is preliminary segregation data in a single family, both the genetic and experimental evidence for PABPC5 in Tourette syndrome are currently limited. Further replication in independent cohorts and targeted functional studies are required for a more definitive clinical interpretation.
Key take‑home: Although an Xq21.31 microduplication encompassing PABPC5 has been observed in a family with Tourette syndrome, the limited genetic evidence and lack of supportive functional data necessitate caution before its routine clinical adoption in diagnostic practice.
Gene–Disease AssociationLimitedThe association is based on a single family with three affected siblings (including the proband) and one unaffected sibling, providing limited segregation evidence (PMID:23894120). Genetic EvidenceLimitedA single case series identified an Xq21.31 microduplication involving PABPC5 in three affected males, indicating preliminary genetic support though limited by the absence of additional independent probands (PMID:23894120). Functional EvidenceLimitedNo gene-specific functional assays, repair/rescue experiments, or animal models have been reported to elucidate the mechanism by which altered PABPC5 dosage might lead to Tourette syndrome. |