A novel mutation in the 12(R)‐lipoxygenase (ALOX12B) gene underlies nonbullous congenital ichthyosiform erythroderma

Inherited ichthyoses are disorders of cornification that broadly refer to a group of heterogeneous skin disorders characterized clinically by generalized scaling. Among these, autosomal recessive congenital ichthyosis is a subgroup comprising three major types of ichthyosis, i.e. nonbullous congenital ichthyosiform erythroderma (NCIE, MIM 242100), lamellar ichthyosis (LI, MIM 242300) and harlequin ichthyosis (MIM 242500), together with several other ichthyosis syndromes. Until the 1980s, LI was the term used to describe both LI and NCIE. However, since that time, LI and NCIE have been separated into two distinct clinical disorders. Although the classic clinical features of LI and NCIE can be used to distinguish the two disorders, many patients show an intermediate or overlapping phenotype, making the classification of these patients challenging on the basis of clinical findings alone. Patients with LI classically have large, dark plate-like scales involving the entire body surface, toughness of the facial skin leading to ectropion and eclabium, and secondary nail deformity. Scarring alopecia is another characteristic of LI, especially at the periphery, because of traction at the hairline. Patients do not usually improve with age although they have a normal life span. In contrast to LI, NCIE is classically characterized by generalized erythema and fine white scales. An affected child is frequently born as a collodion baby. Mild ectropion, eclabium or alopecia are common and the palms and soles are hyperkeratotic. In some cases, improvement occurs during childhood and puberty. Recent genetic studies have revealed extensive locus heterogeneity underlying the ichthyoses. Thus far, nine genetic loci (Table 1) have been identified that contain the candidate genes for LI and NCIE. Four loci have been assigned for LI and the genes for two of these loci are known, TGM1 (14q11.2) and ABCA12 (2q34). Interestingly, a mutation in the ABCA12 (2q34) gene has recently been found also to underlie harlequin ichthyosis. Furthermore, mutations in TGM1 can also result in NCIE, making direct genotype–phenotype correlations a challenge. Other genes responsible for NCIE are CGI58 and ichthyin. Recently, mutations in the lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes have been found to underlie the NCIE phenotype. In this study, we report a novel homozygous missense mutation, R488H, in ALOX12B, in a patient affected with NCIE. Case and methods