ABCMdb

PMID: 18284401

Akiyama M, Sakai K, Hatamochi A, Yamazaki S, McMillan JR, Shimizu H
Novel compound heterozygous nonsense and missense ABCA12 mutations lead to nonbullous congenital ichthyosiform erythroderma.
Br J Dermatol. 2008 Apr;158(4):864-7. Epub 2008 Feb 16., [PubMed]

Sentences

No. Mutations Sentence Comment

31 ABCA12 p.Gly1136Asp In the classic NBCIE phenotype, the entire body is covered in fine, white scales over a background of erythrodermic skin.1 Mutations in ABCA12 are known to underlie harlequin ichthyosis (HI)2 and lamellar ichthyosis (LI).3 ABCA12 is a member of a large superfamily of ATP-binding cassette (ABC) transporters, which bind and hydrolyze ATP to transport various molecules across a limiting membrane or into a vesicle.4 The ABCA subfamily members are all thought to be lipid transporters.5 Lack of ABCA12 function subsequently leads to disruption of lamellar granule lipid transport in the upper keratinizing epidermal keratinocytes resulting in malformation of the stratum corneum intercellular lipid layers.2 Here we report that a compound heterozygote harbouring two novel ABCA12 mutations, c.3407G>A (p.Gly1136Asp) and c.5005C>T (p.Gln1669X), exhibited a typical NBCIE phenotype. Login to comment 40 ABCA12 p.Gly1136Asp Oligonucleotide primers and polymerase chain reaction conditions used for amplification of all ABCA12 exons and exon-intron borders were originally derived from the report by Lefe`vre et al.3 and were partially modified for the present study.2 In the patient, a combination of two novel heterozygous ABCA12 mutations, c.3407G>A (p.Gly1136Asp) in exon 24 and a novel nonsense mutation c.5005C>T (p.Gln1669X) in exon 33, were identified (sequence according to GenBank accession no. Login to comment 44 ABCA12 p.Gly1136Asp According to the molecular structure of ABCA12,6 the paternal missense mutation c.3407G>A (p.Gly1136Asp) in exon 24 leads to a substitution of a glycine residue at codon position 1136 to an aspartic acid residue, effecting an intracytoplasmic region between the second and the third ABCA12 transmembrane domains. Login to comment 49 ABCA12 p.Gly1136Asp mutation p.Gly1136Asp is close to the second transmembrane domain. Login to comment 56 ABCA12 p.Thr345Pro In general, homozygotes or compound heterozygotes harbouring ABCA12 truncation mutations usually exhibit an HI phenotype.2,7-9 To date, nine LI families have been reported to harbour ABCA12 mutations and all the patients were either homozygotes (eight families) or compound heterozygotes (one family) for missense mutations located in the first ATP-binding cassette.3 Only two patients with ABCA12 mutations have been reported to show a NBCIE phenotype.10 Mutations on both alleles were shown only in one patient out of the two.10 The patient was a homozygote for the missense mutation p.Thr345Pro affecting neither the ATP-binding cassette nor the transmembrane domain.10 The present NBCIE patient also had a missense mutation separate from the ATP-binding cassettes and the transmembrane domains on one allele, although a nonsense mutation ablating one ATP-binding cassette was found on the other allele. Login to comment