Several mutations in the ABCA12 gene are known to cause harlequin-type ichthyosis. Most of these mutations are predicted to lead to an absence of ABCA12 protein or the production of an extremely small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein causes numerous problems with the development of the epidermis before and after birth. Abnormalities in lipid transport prevent the skin from forming an effective barrier and result in the hard, thick scales characteristic of harlequin ichthyosis.
Mutations in the ABCA12 gene also cause another severe skin disorder, lamellar ichthyosis type 2. People with this disorder have red, scaly, plate-like skin covering most of their bodies. The ABCA12 mutations that cause this disorder substitute one amino acid (a building block of proteins) for another amino acid in the ABCA12 protein. These mutations almost always occur in an important functional region of the protein (the region that binds to ATP, a molecule that supplies energy for chemical reactions). Changes in the structure of the ABCA12 protein likely disrupt its ability to transport lipids, which affects the development of skin before and after birth.
^Annilo T, Shulenin S, Chen ZQ, Arnould I, Prades C, Lemoine C, Maintoux-Larois C, Devaud C, Dean M, Denefle P, Rosier M (2002). "Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34". Cytogenet Genome Res. 98 (2–3): 169–76. PMID12697999. doi:10.1159/000069811.
^Lefevre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J (2003). "Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2". Hum Mol Genet. 12 (18): 2369–78. PMID12915478. doi:10.1093/hmg/ddg235.
Lefévre C, Audebert S, Jobard F, Bouadjar B, Lakhdar H, Boughdene-Stambouli O, Blanchet-Bardon C, Heilig R, Foglio M, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J (September 2003). "Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2". Hum. Mol. Genet. 12 (18): 2369–78. PMID12915478. doi:10.1093/hmg/ddg235.*Sakai K, Akiyama M, Sugiyama-Nakagiri Y, et al. (2007). "Localization of ABCA12 from Golgi apparatus to lamellar granules in human upper epidermal keratinocytes". Exp. Dermatol. 16 (11): 920–6. PMID17927575. doi:10.1111/j.1600-0625.2007.00614.x.
Thomas AC, Sinclair C, Mahmud N, et al. (2008). "Novel and recurring ABCA12 mutations associated with harlequin ichthyosis: implications for prenatal diagnosis". Br. J. Dermatol. 158 (3): 611–3. PMID17986308. doi:10.1111/j.1365-2133.2007.08277.x.
Dean M, Rzhetsky A, Allikmets R (2001). "The human ATP-binding cassette (ABC) transporter superfamily". Genome Res. 11 (7): 1156–66. PMID11435397. doi:10.1101/gr.184901.
Jiang YJ, Lu B, Kim P, et al. (2008). "PPAR and LXR activators regulate ABCA12 expression in human keratinocytes". J. Invest. Dermatol. 128 (1): 104–9. PMID17611579. doi:10.1038/sj.jid.5700944.
Ohkubo T, Shibata N, Ohnuma T, et al. (2005). "No genetic association between ATP binding cassette proteins and Japanese sporadic Alzheimer's disease". Dement Geriatr Cogn Disord. 20 (2–3): 95–8. PMID15980630. doi:10.1159/000086473.
Annilo T, Shulenin S, Chen ZQ, et al. (2002). "Identification and characterization of a novel ABCA subfamily member, ABCA12, located in the lamellar ichthyosis region on 2q34". Cytogenet. Genome Res. 98 (2–3): 169–76. PMID12697999. doi:10.1159/000069811.
Parmentier L, Clepet C, Boughdene-Stambouli O, et al. (1999). "Lamellar ichthyosis: further narrowing, physical and expression mapping of the chromosome 2 candidate locus". Eur. J. Hum. Genet. 7 (1): 77–87. PMID10094194. doi:10.1038/sj.ejhg.5200271.
Natsuga K, Akiyama M, Kato N, et al. (2007). "Novel ABCA12 mutations identified in two cases of non-bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia". J. Invest. Dermatol. 127 (11): 2669–73. PMID17508018. doi:10.1038/sj.jid.5700885.
Sakai K, Akiyama M, Yanagi T, et al. (2009). "ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma". J. Invest. Dermatol. 129 (9): 2306–9. PMID19262603. doi:10.1038/jid.2009.23.
Allikmets R, Gerrard B, Hutchinson A, Dean M (1996). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum. Mol. Genet. 5 (10): 1649–55. PMID8894702. doi:10.1093/hmg/5.10.1649.