Identification of two novel mutations in the PLCD1 gene in Chinese patients with hereditary leukonychia

Abstract

Hereditary leukonychia (HL) is a rare nail dystrophy disease, and several different clinical manifestations and mutations in the phospholipase C δ 1 (PLCD1) gene have been reported. The present study reports on one Chinese family and one sporadic case of with HL. The family members exhibited an autosomal dominant pattern of inheritance with the involvement of all the fingers and toenails in all the patients. Of interest, most of the affected members had koilonychia during their childhood. Thus, the present study first used gene mapping with an aim to identify the pathogenic gene underlying koilonychia. Through genome-wide linkage analysis, the pathogenic area of koilonychia was identified on chromosome 3 with multipoint Log of Odds scores >2. A novel pathogenic mutation c.1384G>A (p.E462K) was identified in the PLCD1 gene in all the patients in the family, which confirmed the diagnosis of hereditary leukonychia. A novel mutation c.770G>A (p.R257H) was also detected in one sporadic case of leukonychia. On the basis of these findings and of previous studies, it is suggested that hereditary leukonychia may initially present as koilonychia, whereas hereditary koilonychia does not progress to leukonychia. Moreover, the present study identified two pathogenic variants of the PLCD1 associated with hereditary leukonychia, and highlights the significance of genetic diagnosis.

Identification of a novel homozygous missense mutation in the Phospholipase C, delta-1 gene associated with leukonychia in a Middle Eastern patient

“…Our patient had leukonychia associated with a homozygous missense mutation in the PLCD1 gene. PLCD1, a key enzyme in the cellular signaling pathway, has 15 exons, 1 and is localized and abundant in the human nail matrix using proteomic analysis. 3 …”

“…Using genome-wide linkage analysis, Shen et al 1 identified 2 novel mutations in PLCD1 in a Chinese family with HL ( Table I ). All 6 patients (2 males and 4 females) presented with koilonychia in childhood, and 5/6 patients had distal brown discoloration of their nails.…”

“…All 6 patients (2 males and 4 females) presented with koilonychia in childhood, and 5/6 patients had distal brown discoloration of their nails. 1 One patient had a sporadic case of leukonychia with koilonychia with mutation c.770G > A (p.R257H) ( Table I ). 1 In another study examining HL in a Chinese Han pedigree with 2 affected individuals (mother and son), whole-exome sequence analysis identified a new missense mutation in exon 9 of the PLCD1 gene ( Table I ).…”

“… 2 Some cases are due to Phospholipase C, delta-1 (PLCD1) gene mutations, encoding an enzyme regulating energy metabolism signaling, Ca 2+ homeostasis, and intracellular movement. 1 We present a case of leukonychia associated with a novel homozygous missense PLCD1 gene mutation.…”

“…Hereditary leukonychias (HLs) are rare nail disorders that present with partial or complete nail plate whitening, 1 , 2 due to abnormal keratinization of distal nail matrix cells, with numerous intracellular vacuoles with less dense keratin that appear white with light reflection. 2 Some cases are due to Phospholipase C, delta-1 (PLCD1) gene mutations, encoding an enzyme regulating energy metabolism signaling, Ca 2+ homeostasis, and intracellular movement.…”