Novel ABCA12 Mutations Identified in Two Cases of Non-Bullous Congenital Ichthyosiform Erythroderma Associated with Multiple Skin Malignant Neoplasia

ABCA12 mutations and autosomal recessive congenital ichthyosis: A review of genotype/phenotype correlations and of pathogenetic conceptsa

“…Fig. S1B) were also reported to harbor ABCA12 mutations as the causative genetic defect Natsuga et al, 2007;Sakai et al, 2009]. To date, 10 ABCA12 mutations have been reported in eight CIE families.…”

“…In contrast, CIE and LI are both heterogeneous genetic disorders and several causative or underlying molecules including ABCA12 have been identified [Jobard et al, 2002;Lefèvre et al, 2003Lefèvre et al, , 2004Lefèvre, 2006]. Mutations in six genes have been described in non-HI ARCI to date, including TGM1 [Huber et al, 1995;Russell et al, 1995], ABCA12 [Lefèvre et al, 2003;Natsuga et al, 2007], NIPAL4 (also known as ICHTHYIN) [Lefèvre et al, 2004], CYP4F22 [Lefèvre, 2006], ALOX12B and ALOXE3 [Jobard et al, 2002]. Among them, TGM1 is thought to be the most prevalent causative gene [Fischer, 2009;Herman et al, 2009].…”

“…ABCA12 (MIM] 607800) missense mutations leading to defects in the ATP-binding cassette were reported in LI cases (type 2 LI [MIM] 601277]) [Lefèvre et al, 2003] and ABCA12 truncation mutations were reported underlying HI patients Kelsell et al, 2005]. Recently, we reported that ABCA12 missense mutations are a major cause of CIE cases in the Japanese population Natsuga et al, 2007;Sakai et al, 2009]. Thus, ABCA12 mutations lead to all three ARCI clinical phenotypes including HI, LI and CIE and ABCA12 mutations are highlighted as one of the major causes of ARCI.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…We propose that ''ARCI'' should be used to refer to harlequin ichthyosis (HI) and disorders of the LI/CIE phenotypic spectrum (Table V) exclusively. HI (Fig 2, A) was included, because functional null mutations in the ABCA12 gene cause the disease, 15,16 whereas missense mutations in the same gene may result in a milder phenotype that shows collodion membrane at birth and develops into LI 17,18 or CIE, 19,20 often with palmoplantar keratoderma (PPK). Those infants with HI who survive the perinatal period go on to express a severe and very scaling erythroderma 21 ( Fig 2, B and C ).…”

“…28 At least 22% of these cases did not exhibit mutations in any of the known ARCI genes, 27 implying that further loci must exist, such as two loci on chromosome 12p11.2-q13. 29,30 A preliminary clinicogenetic correlation based on the [17][18][19][20] and our discussions at the consensus conference is given in Tables II and III. LI is characterized by coarse and brown/dark scaling (Fig 2, E and F ). Affected individuals are often born with collodion membrane and pronounced ectropion (Fig 2, D).…”