159 Congenital leukonychia caused by a mutation in the GJB2 gene

Abstract

Congenital leukonychia is a rare nail disorder with white appearance of nails. PLCD1 is considered as causative gene and congenital leukonychia with PLCD1 mutation shows either autosomal dominant or recessive inheritance trait. While leukonychia was also observed in the patients with hearing loss caused by the variant in GJB2. In the family, there are patients with leukonychia without hearing loss, while other unrelated patients who suffer only from hearing loss also exist. To the best our knowledge, only one case of leukonychia caused by GJB2 gene has been reported. A 13-year-old girl had white nail since birth. Her bilateral 2-5 fingernails showed smooth and white color. Her bilateral toe fingers were observed as mild white color. In addition to nail abnormalities, she did not show any other associated findings and there is no known family history. The pathogenic mutation was not identified in PLCD1. We then performed whole-exome sequencing, and c. 408C>A (p.Tyr136*) and c.134G>A (p.Gly45Glu) in the GJB2 gene were identified. We searched for the mutations in the patient’s parents and the patient’s mother without white nail also had the same 2 variants in GJB2. Based on these findings, 2 variants of the patient in GJB2 exist in the same allele originated from the patient’s mother. Previously and our case reports demonstrated that GJB2 variant cause congenital leukonychia. While there are individual without white nail in the family members with GJB2 variant. Therefore, several elements including the GJB2 variants and permeability and/or the modifier of GJB2 gene might be involved with congenital leukonychia. GJB2 gene is involved with various diseases such as KID syndrome and Vohwinkel syndrome and GJB2 related skin and nail disorders are autosomal dominant form. Therefore, the nail condition in our patient was induced by either GJB2 variant. Our case report supported that GJB2 variant cause congenital leukonychia.