ANKDD1B – ankylosing spondylitis

An autosomal dominant inheritance pattern for ankylosing spondylitis (AS) was observed in a single Han Chinese pedigree in which a rare missense variant c.259C>G (p.Leu87Val) co-segregated with all affected male patients (n=5) and showed incomplete penetrance in females (1/5 carriers affected) ([PMID:29976160]). A second distinct missense variant p.Arg102Leu was identified in a unrelated early-onset male AS patient and both variants were absent in 500 ethnically matched controls, suggesting a role for ANKDD1B in AS pathogenesis ([PMID:29976160]). No functional assays or animal models have been reported to date assessing the impact of these variants on protein function or AS-related pathways.

Given only a single pedigree and one sporadic case totaling 2 probands ([PMID:29976160]) without experimental validation or replication in independent cohorts, the clinical validity of ANKDD1B in AS remains limited. Additional genetic studies and functional experiments are required to establish a definitive gene–disease relationship.

Key Take-home: ANKDD1B missense variants have been observed in two AS cases with segregation in one family, but evidence is currently insufficient for clinical diagnostic utility.

References

• BMC Medical Genetics • 2018 • Identification of ANKDD1B variants in an ankylosing spondylitis pedigree and a sporadic patient. PMID:29976160

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