ABCMdb

PMID: 20661612

Matsukawa T, Asheuer M, Takahashi Y, Goto J, Suzuki Y, Shimozawa N, Takano H, Onodera O, Nishizawa M, Aubourg P, Tsuji S
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes.
Neurogenetics. 2011 Feb;12(1):41-50. Epub 2010 Jul 27., [PubMed]

Sentences

No. Mutations Sentence Comment

59 ABCD1 p.Gly277Arg Results Resequencing DNA microarray-based mutational analysis of ABCD1 gene in Japanese ALD patients All the mutations of ABCD1 were clearly identified using the resequencing DNA microarray system including 26 missense, 2 nonsense, and 12 insertion/deletion mutations G277R (1215 G>A) Patient AScan data of the A C Scan data of the resequencing DNA G T resequencing DNA microarray (TKYPD01) T microarray (TKYPD01) Sequence data of theSequence data of the direct nucleotidedirect nucleotide sequence analysissequence analysis Control AScan data of the A C Scan data of the resequencing DNA G T q g microarray (TKYPD01) T Sequence data of the di l iddirect nucleotide sequence analysis Fig. 2 Scan data of the resequencing DNA microarray and sequence data of the direct nucleotide sequence analysis (upper panel: patient, lower panel: control). Login to comment 61 ABCD1 p.Gly277Arg Here, a mutation (G277R) was detected, and the signal intensities around the mutation were reduced because of the mismatch of the mutation site. Login to comment 74 ABCD1 p.Trp595* ABCD1 p.Trp595* The five known SNPs (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801) were in complete Table 1 Identified ABCD1 mutations: mutations of ABCD1 that result in devastating effects (frame shifts or nonsense mutations) on adrenoleukodystrophy protein (ALDP) Patient number Phenotype Mutation of ABCD1 Effect of mutation of ABCD1 1 CCALD 488C>AT Frameshift at P34 2 CCALD 2171G>A W595X 3 CCALD 5'UTR-Ex2 1.4-kb deletiona Disruption of gene structure 4 AdultCer Del. 986Ca Frameshift at D200 5 AdultCer Del. 1801-1802AGa Frameshift at Q472 6 AMN-Cer Del. 2251 GGTG ins. TGTTCTa Frameshift at R622 7 AMN Ins. 1237Ta Frameshift at Y281 8 AMN Del. 1801-1802AGa Frameshift at Q472 9 AMN 2171G>A W595X 10 AMN Del. 2251 GGTG ins. TGTTCTa Frameshift at R622 11 Unknown Del. 1541Ca Frameshift at F385 12 Unknown Ex8-10 0.3-kb deletiona Disruption of gene structure Amino acid residue numbers in ALDP are based on Mosser et al. [1]. Login to comment 84 ABCD1 p.Pro560Leu ABCD1 p.Pro560Leu ABCD1 p.Arg660Trp ABCD1 p.Arg518Trp ABCD1 p.Asn148Ser ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Arg518Gln ABCD1 p.Glu609Lys ABCD1 p.Gly277Arg ABCD1 p.His667Asn ABCD1 p.His667Asn ABCD1 p.Ala616Asp ABCD1 p.Phe540Ser ABCD1 p.Ser290Trp ABCD1 p.Arg401Trp ABCD1 p.Gln544Arg ABCD1 p.Gln544Arg ABCD1 p.Pro84Ser ABCD1 p.Glu271Lys ABCD1 p.Asn214Asp ABCD1 p.Ser108Leu ABCD1 p.Ser108Leu ABCD1 p.Ser108Leu ABCD1 p.Thr254Pro ABCD1 p.Leu313Pro Interestingly, the five previously described SNPs (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801) that are in complete linkage disequilibrium were significantly less frequently represented in the patients with Japanese AMN than in the controls in the Japanese population (p=0.0468), whereas Table 2 Identified ABCD1 mutations: mutations of ABCD1 that result in amino acid substitutions or in-frame deletions Patient number Phenotype Mutation of ABCD1 Effect of mutation of ABCD1 Position of mutation 13 CCALD 709C>T S108L Loop1 14 CCALD 709C>T S108L Loop1 15 CCALD 829A>G N148S TM2 16 CCALD 1026A>G N214D TM3 17 CCALD 1182G>A G266R Between TM4 and EAA-like 18 CCALD 1324T>Ca L313P Between EAA-like and TM5 19 CCALD 1938C>T R518W Walker A 20 CCALD 1939G>A R518Q Walker A 21 CCALD 2017A>G Q544R Between Walker A and Cons 22 CCALD 2017A>G Q544R Between Walker A and Cons 23 CCALD 2065C>T P560L Between Walker A and Cons 24 CCALD 2065C>T P560L Between Walker A and Cons 25 CCALD Del. 2145-2156 Del. HILQ587-590 Between Walker A and Cons 26 AdultCer Del. 1257-1259 Del.E291 EAA-like 27 AdultCer 2005T>C F540S Between Walker A and Cons 28 AdultCer 2358C>T R660W C-terminal to Walker B 29 AdultCer 2385C>A H667N C-terminal to Walker B 30 AMN-Cer 1146A>C T254P TM4 31 AMN 636C>T P84S TM1 32 AMN 709C>T S108L Loop1 33 AMN 1182G>A G266R Between TM4 and EAA-like 34 AMN 1197G>A E271K Between TM4 and EAA-like 35 AMN 1215G>Aa G277R Between TM4 and EAA-like 36 AMN 1255C>G S290W EAA-like 37 AMN 1581C>T R401W Between TM6 and Walker A 38 AMN 2233C>A A616D Cons 39 AMN 2385C>A H667N C-terminal to Walker B 40 Asymptomatic 2211G>A E609K Cons Amino acid residue numbers in ALDP are based on Mosser et al. [1]. Login to comment 101 ABCD4 p.Glu368Lys ABCD4 p.Ala304Thr Gene Fragment SNP ID Category Amino acid change ABCD3 Exon1 rs4148058 5' untranslated region Exon2 rs2147794 Intron Exon3 rs16946 Coding synonymous Exon7 rs681187 Intron Exon23 rs662813 3' untranslated region Exon23 rs337592 3' untranslated region ABCD4 5'UTR rs17782508a Upstream at the transcription start site Intron1 rs17182959 Intron Intron1 rs17158118 Intron Exon3 rs2301345a Coding synonymous L62L Exon9 rs4148077a Coding nonsynonymous A304T Exon10 rs4148078a Coding synonymous L320L Exon11 rs3742801a Coding nonsynonymous E368K Table 4 Summary of identified single nucleotide polymorphism (SNPs) of ABCD2, ABCD3, and ABCD4 in 40 adrenoleukodystrophy patients: known SNPs A total of 24 SNPs of ABCD2, ABCD3, and ABCD4 were identified in 40 ALD patients. Among them, 11 SNPs (45.8%) were novel SNPs. Login to comment 108 ABCD4 p.Glu368Lys ABCD4 p.Ala304Thr Among the SNPs with suggestive association in the Japanese patients (rs17782508, rs2301345, rs4148077, rs4148078, and rs3742801), rs4148077 (A304T) substitutes a hydrophilic amino acid for a hydrophobic amino acid, and rs3742801 (E368K) substitutes a basic amino acid for an acidic amino acid. Login to comment