ABCA12 Mutation

Till Sep’2010, 56 ABCA12 mutations have been described (online database: http://www.derm-hokudai.jp/ABCA12/) in 66 unrelated families including 48 Harlequin Ichthyosis (HI), 10 Lamellar Ichthyosis (LI) and 8 Congenital Ichthyosiform Erythroderma (CIE) families. Mutations have been reported among ARCI (Autosomal Recessive Congenital Ichthyosis) patients with African, European, Pakistani/Indian, and Japanese backgrounds, from almost all over the world. Of the 56 mutations, 36% (20) are nonsense, 25% (14) are missense, 20% (11) comprise small deletions, 11% (6) are splice site, 5% (3) are large deletions, and 4% (2) are insertion mutations. At least, 62.5% (35) of the total reported mutations are predicted to result in truncated proteins. There is no apparent mutation hot spot in ABCA12, although mutations underlying LI phenotype are clustered in the region of the first ATP-binding cassette.

The most common reported mutation in ABCA12 is c.7322delC (p.Val2442SerfsTer28) in exon 49, which has been reported in 7 HI families with Pakistani background. This mutation has been identified only in the Pakistani population. Thomas et al. (2008) reported that 80% of HI patients and parents (10 screened) originated from the Pakistani/Indian area had the mutation 7322delC.

The second most common reported ABCA12 mutation is a missense mutation p.Asn1380Ser in Walker A motif of the first ATP-binding cassette, which is essential for the transporter function of ABCA12. This missense mutation p.Asn1380Ser has been identified in 5 LI families from Africa (3 families from Morocco and 2 families from Algeria).

Out of further 10 different ABCA12 mutations; each mutation has been identified in two unrelated families from certain geographic regions. Among these 10 mutations, 5 ABCA12 mutations — c.2021_2022del2, c.3295_2A4G, p.Thr1387del, p.Arg1950Ter, and p.Arg2482Ter — were found in 2 independent patients from Japan.

As for the other five mutations — p.Trp1294Ter, p.Gly1651Ser, p.Tyr1090Ter, c.2025delG, and p.Trp1744Ter — were found in two independent families with Pakistani, Algeria, Albanian/Bosnian, Anglo-Saxon and native origins, respectively.