Hereditary 'white nails': a genetic and structural study

Abstract

Genetic linkage indicates that the gene defect underlying the leuconychia in the family studied resides on chromosome 12q13. As the type II keratins map within this chromosomal interval, it is possible that a mutation in one of these keratin genes may be a cause of the hereditary leuconychia. The white appearance of nails in this disease seems to be due to an abnormal keratinization of cells originating from the proximal nail matrix, leading to the presence of abundant intracellular vacuoles and to a lesser compactness of keratins.

Ten bright-white fingernails in two young healthy patients

“…Congenital leuconychia, either total or subtotal, is not only extremely rare but is usually hereditary, with an autosomal dominant inheritance pattern. The responsible gene has been mapped to chromosome 12q13, where the genes for type II cytokeratins and hard keratins are located 6 …”

“…Histologically, the main feature of leuconychia is abnormal hypergranulosis on the proximal nail matrix and the presence of abundant vacuoles and the separation between the keratin filament bundles within the nail plate, which lead to chromatic changes in the nails 6 …”

A family with leukonychia totalis

“…[2–4] Genetic evaluation on four generations of a French family with hereditary leukonychia as a sole congenital anomaly and autosomal dominant pattern of inheritance provided evidence of linkage to chromosome 12q13, a region which contains the basic type II keratins locus. [5]…”

Identification of a novel PLCD1 mutation in Chinese Han pedigree with hereditary leukonychia and koilonychia

“…PLC selectively catalyzes the hydrolysis of the phospholipid, phosphatidylinositol 4,5‐bisphosphate (PIP 2 ), and release diacyl glycerol (DAG), inositol 1,4,5‐trisphosphate (IP 3 ), which mediates the activation of protein kinase C (PKC), and binding of the IP3 receptors (IP3Rs), respectively, to open the intrinsic cation channel and release calcium ions from the intracellular pool . There are 13 types of mammalian phospholipase C that are classified into six isotypes based on structure, activation, and distinct subcellular distribution .…”

“…Subsequent studies on Plcd1 and malnutrition in nude mice further suggest that dysregulation of PLCD1 may lead to dystrophy nail, shorter nails and abnormal shape, severe parakeratosis of dorsal nail plate, impaired keratinization of nail matrix, and reduced deck sulfur concentrations . Although a number of cases have delineated the frequency and scope of hereditary leukonychia with PLCD1 mutations as reported in Jordanian and Pakistani, few have provided the information of genotype‐phenotype correlations. The association between hereditary leukonychia patients in East Asians and PLCD1 is unclear.…”