Study identifies genetic cause for yellow nail syndrome

The median age for onset of symptoms for those with sYNS was 12 years. Yellow nails and lung disease were the presenting symptoms in most patients with YNS. The researchers examined next generation sequencing data for all patients with YNS to identify and analyze genetic variants. CELSR1 was highlighted as the principal candidate disease-causing gene with autosomal recessive inheritance. The researchers found that all but one patient with cYNS had biallelic variants in CELSR1.

The remaining patient had a heterozygous loss-of-function variant in FZD6. Both CELSR1 and FZD6 are core molecules in the Wnt/PCP pathway. None of the patients with sYNS had candidate variants in either CELSR1 or FZD6.

The researchers then extracted RNA from all patients to assess the Wnt/PCP pathway expression, and found that the pathway is disrupted both in cYNS patients with genetic variants and, to a lesser degree, in sYNS patients without genetic defects. These results suggest a strong case for the involvement of Wnt/PCP signaling and PCP defects in the pathogenesis of YNS.

Reference:

Alina Kurolap, Chofit Chai Gadot, Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome, Annals of Internal Medicine,  https://doi.org/10.7326/ANNALS-24-01101