@article{Alsultan_Bukhari_Vatte_Bin Nooh_Alsamman_2026, place={Fidenza, Italy}, title={RSPO4 in anonychia congenita: Evidence of segregation without causation}, volume={97}, url={https://mattioli1885journals.com/index.php/actabiomedica/article/view/18509}, DOI={10.23750/abm.2026.18509}, abstractNote={
Background: Anonychia congenita is a rare autosomal recessive disorder characterized by complete absence of fingernails and toenails, often without associated physical or mental abnormalities. RSPO4 gene mutations are a known genetic cause which plays a crucial role in the Wnt signaling pathway. Methods: We examined a consanguineous family from Saudi Arabia with multiple individuals affected by nonsyndromic anonychia. Sanger confirmation identified a variant in exon 3 of RSPO4. Pedigree segregation analysis and electropherogram comparisons were performed. Results: The homozygous missense variant c.317G>A (p.Arg106Gln) in RSPO4 was identified in all affected individuals. However, this variant is reported in ClinVar (VCV000784403.4) as likely benign and has a global allele frequency of approximately 2.1% in gnomAD. In silico pathogenicity predictions and population-scale genomic evidence argue against its role as a causative mutation. Conclusion: Despite its segregation with the anonychia phenotype in the family, the c.317G>A variant in RSPO4 is unlikely to be pathogenic. This finding underscores the importance of integrating public genomic databases and in silico tools to avoid false-positive causal associations, especially in consanguineous pedigrees. Further analysis, including whole-genome sequencing and transcriptomic studies are required to identify the true pathogenic variants.
}, number={4}, journal={Acta Biomedica Atenei Parmensis}, author={Alsultan, Afnan and Bukhari, Iqbal and Vatte, Chittibabu and Bin Nooh, Deemah and Alsamman, Khaldoon}, year={2026}, month={Aug.}, pages={18509} }