SG02 First report of ABCA12 mutations causing isolated palmoplantar keratoderma and a review of mild phenotypes associated with ABCA12

This report presents a case of isolated palmoplantar keratoderma (PPK) resulting from mutations in the C-terminus of ABCA12, and reviews the reported mild cases associated with ABCA12 mutations. A 31-year-old female patient presented with progressive thickening of the palms and soles since the age of 7 years, with no obvious conscious symptoms. No rashes of ichthyosis were noted on other areas of the body, and no abnormalities of the nails, hair and teeth were identified. Genetic analysis identified a novel compound heterozygous ABCA12 gene mutation in the patient. This included a mutation c.7659_7662dupGAGT (p.Q2555Efs*20) in exon 52 and c.7386G>C (p.M2462I) in exon 50, inherited from her mother and father, respectively. The diagnosis of isolated PPK associated with ABCA12 variants was considered. Pathogenic variants in ABCA12 are important causative genetic defects for autosomal recessive congenital ichthyoses, encompassing conditions such as congenital ichthyosiform erythroderma (CIE; MIM #601277), harlequin ichthyosis (#242500) and lamellar ichthyosis, often accompanied by PPK. Occasionally, specific ABCA12 mutations have been linked to milder phenotypes, including erythrokeratodermia variabilis et progressiva (EKVP) and pityriasis rubra pilaris (PRP) (Table) (Sun Q, Burgren NM, Cheraghlou S et al. The genomic and phenotypic landscape of ichthyosis: an analysis of 1000 kindreds. JAMA Dermatol 2022; 158: 16–25; Takeichi T, Hamada T, Yamamoto M et al. Patients with keratinization disorders due to ABCA12 variants showing pityriasis rubra pilaris phenotypes. J Dermatol 2024; 51: 101–5). In our study, PPK without lesions of generalized ichthyosis was noted. The identified causal mutations, located in exons 50 and 52, indicate a potential mild loss of protein function in the C-terminus of ABCA12, offering a plausible explanation for the observed mild phenotype. Our study expands the phenotypic spectrum associated with ABCA12 variants and underscores the genetic heterogeneity of isolated PPK.TableABCA12-associated mild keratinization disordersClinical phenotypeGenetic basisEKVPCompound heterozygous: p.N678Rfs*10; c.2866–8T>ACompound heterozygous: p.D844G;p.P1938SCompound heterozygous: p.Y1929*; p.E2284DCompound heterozygous: H1471R; T1534PRPHomozygous: p.T1534MHomozygous: p.R2426WNaevoid form of CIERecessive mosaicism: p.l1257Nfs*4; p.E1227KMild CIE with periodic exacerbationCompound heterozygous: p.N2184I; p.I2307Rfs*14Isolated PPKCompound heterozygous: p.Q2