Homozygous Missense Variant in the Solute Carrier Organic Anion Transporter 2A1 () Gene Underlies Isolated Nail Clubbing.

BACKGROUND

Inherited isolated nail clubbing is a very rare Mendelian condition in humans, characterized by enlargement of the terminal segments of fingers and toes with thickened nails. Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the gene and the gene.

OBJECTIVES

An extended Pakistani family having two affected siblings born of unaffected consanguineous union was included in the study. Predominant isolated congenital nail clubbing (ICNC) without any other systemic abnormalities was observed, which we aimed to characterize at clinico-genetic level.

METHODS

Whole exome coupled with Sanger sequencing were employed to uncover the sequence variant as a cause of the disease. Furthermore, protein modeling was carried out to reveal the predicted possible effect of the mutation at the protein level.

RESULTS

Whole exome sequencing data analysis revealed a novel biallelic sequence variant (c.155T>A; p.Phe52Tyr) in the gene. Further, Sanger sequencing analysis validated and confirmed the segregation of the novel variant in the entire family. Subsequently, protein modeling of the wild-type and mutated SLCO2A1 revealed broad-scale change, which might compromise the proteins' secondary structure and function.

CONCLUSION

The present study adds another mutation to the -related pathophysiology. The involvement of in the pathogenesis of ICNC may open exciting perceptions of this gene in nail development/morphogenesis.