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A recent study investigating familial isolated pituitary adenoma in a Brazilian family identified heterozygous variants in several genes, including REXO4, through whole‑exome sequencing (PMID:27245436). In this family, three affected siblings were found, with the REXO4 variant segregating in all cases, supporting a potential role in disease predisposition.
The genetic evidence indicates that the identified REXO4 variant, reported as a heterozygous change, appears in a familial setting with two additional affected relatives beyond the proband. Although the variant (c.123A>T (p.Lys41Asn)) is predicted to be damaging, the evidence is based solely on observations from this single family (PMID:27245436).
The inheritance pattern in this condition is consistent with an autosomal dominant transmission, which fits with the observed segregation of the variant among affected family members. This mode of inheritance aligns with reports in familial isolated pituitary adenoma cases where a single mutant allele may be sufficient to increase disease risk.
While functional assessment studies were mentioned in the overall evidence summary, no detailed experimental data or animal/cellular models were provided specifically to validate the pathogenicity of the REXO4 variant. This lack of robust experimental confirmation limits the strength of the functional evidence available at present.
Overall, the combined genetic evidence from a single family, with the presence of a predicted damaging REXO4 variant and a consistent autosomal dominant pattern, provides limited support for a causative role in familial isolated pituitary adenoma. Nonetheless, this association may offer a valuable lead and warrants further investigation in larger cohorts and with dedicated functional studies.
Key Take‑home: Despite limited evidence, the detection of a recurrent heterozygous REXO4 variant in a familial context highlights its potential clinical utility as a candidate gene for further diagnostic evaluation in familial pituitary adenoma.
Gene–Disease AssociationLimitedBased on a single family with three affected siblings (PMID:27245436), the evidence for an association is limited by the modest number of unrelated probands and insufficient segregation data. Genetic EvidenceLimitedThe REXO4 variant was identified as a predicted damaging heterozygous change in one family, with segregation in two additional affected relatives (PMID:27245436), which falls short of robust genetic evidence. Functional EvidenceLimitedNo detailed functional assays or animal/cellular models were provided to support the pathogenic impact of the REXO4 variant, limiting the experimental evidence. |