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SRP72 and Myelodysplastic Syndrome

The association between SRP72 and myelodysplastic syndrome is supported by limited human genetic evidence complemented by key functional studies. In the seminal study (PMID:22541560), exome sequencing in an autosomal‑dominant family with aplastic anemia/myelodysplasia identified a heterozygous SRP72 mutation. A subsequent independent family with similar inheritance was also reported, with segregation observed in approximately 3 additional affected relatives (PMID:22541560). The genetic evidence is thus limited by the low number of unrelated families, yet the clear autosomal‑dominant inheritance pattern and segregation in affected members provide specificity for the association.

Functional assays further demonstrated that the mutant SRP72 protein, exemplified by the c.620G>A (p.Arg207His) variant, exhibited aberrant cellular localization and impaired interaction with the essential RNA component of the signal recognition particle (PMID:22541560). However, experimental studies in a Srp72‑null mouse model did not fully recapitulate the human hematological phenotype (PMID:31254415), and additional cohort screening in familial cases did not consistently detect SRP72 mutations (PMID:28357685). These discrepancies underscore the need for further investigation, although the current evidence still holds clinical utility for diagnostic decision‑making in a subset of familial myelodysplasia cases.

References

  • American journal of human genetics • 2012 • Exome sequencing identifies autosomal‑dominant SRP72 mutations associated with familial aplasia and myelodysplasia PMID:22541560
  • European journal of haematology • 2019 • Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes PMID:31254415
  • Pathology oncology research : POR • 2018 • Familial Acute Myeloid Leukemia and Myelodysplasia in Hungary PMID:28357685

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

The association is based on two autosomal‐dominant families with segregation of mutations (PMID:22541560), but is limited by the low number of probands and contradictory evidence in animal models (PMID:31254415) as well as negative screening in additional cohorts (PMID:28357685).

Genetic Evidence

Limited

Genetic evidence is derived from two unrelated families exhibiting autosomal‑dominant inheritance and segregation of the c.620G>A (p.Arg207His) variant in affected individuals (PMID:22541560).

Functional Evidence

Moderate

Functional studies demonstrate that the c.620G>A (p.Arg207His) variant results in protein mislocalization and defective RNA binding (PMID:22541560), although the Srp72‑null mouse model did not fully recapitulate the human phenotype (PMID:31254415).