ABCMdb

PMID: 16675967

Akiyama M, Sakai K, Sugiyama-Nakagiri Y, Yamanaka Y, McMillan JR, Sawamura D, Niizeki H, Miyagawa S, Shimizu H
Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity.
J Invest Dermatol. 2006 Jul;126(7):1518-23. Epub 2006 May 4., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCA12 p.Ser387Asn This patient with moderate clinical severity was compound heterozygous for a novel de novo missense mutation 1160G4A (S387N) in exon 10 and a maternal deletion mutation 4158_4160delTAC (T1387del) in exon 28 of ABCA12. Login to comment 6 ABCA12 p.Ser387Asn Conversely, the residue 387 is located outside the known active sites of ABCA12 and S387N is predicted not to lead to a serious functional deficiency in ABCA12. Login to comment 16 ABCA12 p.Ser387Asn In the study of this case, we have found a compound heterozygous ABCA12 combination of mutations, a novel de novo missense mutation, S387N, in exon 10 and a maternal deletion mutation T1387del in exon 28 in a newborn HI baby. Login to comment 20 ABCA12 p.Ser387Asn In addition, the novel mutation S387N was the first reported de novo mutation in ABCA12. Login to comment 33 ABCA12 p.Ser387Asn The mutation 1160G4A transition was a novel missense mutation that changed a serine residue of codon 387 to an asparagine residue (S387N). Login to comment 34 ABCA12 p.Ser387Asn This missense mutation S387N was not found in either in the parent`s (father or mother), although the patient`s mother was heterozygous for the deletion mutation 4158_4160delTAC (Figure 2). Login to comment 35 ABCA12 p.Ser387Asn Thus, the missense mutation S387N was thought to be a de novo mutation and the deletion mutation was a maternal mutation. Login to comment 52 ABCA12 p.Ser387Asn 1160G>A (S387N) 4158_4160delTAC (T1387del) (maternal) a b Patient Control Patient Control Father Mother Father Mother A A A A A A A A A A AA A A A A AA AA A A A A A A A A AA A A A AC C C C C C C CC C C CC C C CCC C C CC C C C CCCT T TTN N N N N N N N N T TTT T T TT T T T T T TT T T T T TTT G GGGGGGGGGGG GG GG G GG G G G G (de novo) TAC TAC Figure 2. Login to comment 54 ABCA12 p.Ser387Asn (a) Direct sequencing revealed a heterozygous 1160G4A transition (a missense mutation S387N) in exon 10 of ABCA12 of the patient, but not in his parents or normal control samples. Login to comment 96 ABCA12 p.Ser387Asn The novel de novo mutation S387N in the present patient is located outside all of the known ABCA12 active transporter sites, within the cytoplasmic domain at N-terminus of ABCA12 polypeptide (Figure 6). Login to comment 98 ABCA12 p.Ser387Asn Thus, one would predict the de novo missense mutation S387N not to lead to a serious ABCA12 functional loss. Login to comment 111 ABCA12 p.Ser387Asn The present novel missense mutation S387N in our case was the first de novo mutation reported in ABCA12. Login to comment 118 ABCA12 p.Ser387Asn Briefly, genomic DNA isolated from peripheral blood was subjected to PCR amplification, followed by direct automated NH2 (de novo) (Maternal) T1387del (exon 28) S387N (exon 10) Cytoplasmicside B A COOH ATP-binding cassettes A B Walker A and B motifs Active transport signature Membrane Figure 6. Login to comment 121 ABCA12 p.Ser387Asn Note that the de novo missense mutation S387N is located in the intracytoplasmic region between the N-terminus and the first transmembrane domain, not in any active sites, and the other, deletion mutation T1387del is within the first ATP-binding cassette, which is thought to be important for ABCA12 lipid transporter activity. Login to comment