ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.

[lamellar ichthyosis]

Mutations in ABCA 12 have been described in autosomal recessive congenital ichthyoses (ARCI ) including harlequin ichthyosis (HI ), congenital ichthyosiform erythroderma (CIE ), and lamellar ichthyosis (LI ). HI shows the most severe phenotype . CIE and LI are clinically characterized by fine , whitish scales on a background of erythematous skin , and large , thick , dark scales over the entire body without serious background erythroderma , respectively . To date , a total of 56 ABCA 12 mutations have been reported in 66 ARCI families including 48 HI , 10 LI , and 8 CIE families of African , European , Pakistani /Indian , and Japanese origin (online database : http ://www .derm-hokudai .jp /ABCA 12 /). A total of 62 .5 % of reported ABCA 12 mutations are expected to lead to truncated proteins . Most mutations in HI are truncation mutations and homozygous or compound heterozygous truncation mutations always results in HI phenotype . In CIE families , at least one mutation on each allele is typically a missense mutation . Combinations of missense mutations in the first ATP-binding cassette of ABCA 12 underlie the LI phenotype . ABCA 12 is a keratinocyte lipid transporter associated with lipid transport in lamellar granules , and loss of ABCA 12 function leads to a defective lipid barrier in the stratum corneum , resulting in an ichthyotic phenotype . Recent work using mouse models confirmed ABCA 12 roles in skin barrier formation .

Diseases
Validation

Diseases presenting "ichthyosis" symptom

child syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

harlequin ichthyosis

hirschsprung disease

junctional epidermolysis bullosa

kallmann syndrome

lamellar ichthyosis

This symptom has already been validated