ABCMdb

PMID: 12175782

Guimaraes CP, Lemos M, Sa-Miranda C, Azevedo JE
Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene.
Mol Genet Metab. 2002 May;76(1):62-7., [PubMed]

Sentences

No. Mutations Sentence Comment

66 ABCD1 p.Arg660Trp ABCD1 p.Arg660Trp ABCD1 p.Arg518Trp ABCD1 p.Arg518Trp ABCD1 p.Ser108Trp ABCD1 p.Ser108Trp ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Arg518Gln ABCD1 p.Arg518Gln ABCD1 p.Ser108Leu ABCD1 p.Ser108Leu ABCD1 p.Arg591Trp ABCD1 p.Arg591Trp ABCD1 p.Arg545Trp ABCD1 p.Arg545Trp ABCD1 p.His667Leu ABCD1 p.His667Leu ABCD1 p.Gln574* ABCD1 p.Gln574* ABCD1 p.Leu655Pro ABCD1 p.Leu655Pro ABCD1 p.Trp601* ABCD1 p.Trp601* ABCD1 p.Leu114Pro ABCD1 p.Leu114Pro ABCD1 p.Ser103Arg Type of genetic alteration Exon RT-PCR fragmenta Nucleotide change Amplicon usedb /RFLP associatedc ALDP (WB) ABCD1 mRNA (NB) References Missense 1 S103R 1 F2 c.309C > G ALDe1A/þCfoI Diminished Detectable [19] 2 S108W 1 - c.323C > G ALDe1B/þRleAI Not done Not done [18] 3 S108L 1 - c.323C > T - Normal Not done [20] 4 L114P 1 F2 c.341T > C ALDe1B/ÀEcoRII Diminished Detectable Novel mutation 5 ½R236H; G512S 1 F3 [c.707G > A; ALDe1C/þNcoI Novel mutation 6 F6 c.1534G > A] ALDe6/þPstI Not detectable Not done [16,17] 6 G266R 1 F3 c.796G > A - Normal Detectable [21] 7 R518W 6 F6 c.1552C > T ALDe6/ÀHpaII Diminished Detectable [22] 8 R518Q 6 F6 c.1153G > A ALDe6/ÀBamHI Diminished Not done [23] 9 R545W 6 - c.1633A > T ALDe6/þTspRI Not done Not done Novel mutation 10 R591W 7 F7 c.1171C > T ALDe7/0;AciI Normal Not done [24] 11 L655P 9 F8 c.1964T > C ALDe8/9/ÀSapId Diminished Detectable Novel mutation 12 R660W 9 F7/F8 c.1978C > T ALDe8/9/þBsrI Diminished Detectable [16,17,25] 13 H667L 10 F8 c.2000A > T ALDe10/þDdeId Diminished Detectable Novel mutation Nonsense 14 Q574X 7 F6 c.1720C > T ALDe7/ÀAlwNI Not detectable Detectable Novel mutation 15 W601X 8 F7 c.1802G > A ALDe8/9/ÀBsrI Not detectable Not detectable [9] Frameshift 16 fs G298 1 F3 [c.893delG; c.894C > T] ALDe1C/ÀNlaIV Not detectable Detectable Novel mutation 17, 18 fs E472 5 F5 c.1415-1416delAG - Not detectable Detectable [21,26,27] Microdeletion 19 F175del 1 F2 c.522-524delCTT d Diminished Detectable Novel mutation Splicing defect 20 Splicing IVS1 - c.900G > A - Not done Not done [10] 21 Splicing IVS7 - c.1760+1G > A - Not done Not done [18] Polymorphism 1, 5 F673F 8 F8 c.2019C > T ÀTaqI - - [28] 1, 2, 5, 11, 13 30 UTR F8 - ÀDrdI - - [27] a RT-PCR fragment (defined according to [10]) which shows heteroduplex molecules in a CSGE analysis. Login to comment 99 ABCD1 p.Leu114Pro L114P. Login to comment 103 ABCD1 p.Leu114Pro The effect of this missense mutation L114P in ALDP levels was determined by immunoblotting. Login to comment 107 ABCD1 p.Arg236His R236H. Login to comment 109 ABCD1 p.Gly512Ser ABCD1 p.Arg236His After sequencing two missense mutations-R236H and G512S-were found. Login to comment 112 ABCD1 p.Arg236His Thus, it cannot be ascertained at this moment whether the R236H alteration (a conservative amino acid substitution) is a disease-causing mutation per se. Login to comment 117 ABCD1 p.Arg545Trp R545W. Login to comment 118 ABCD1 p.Arg545Trp R545W. Login to comment 122 ABCD1 p.Leu655Pro L655P. Login to comment 123 ABCD1 p.Leu655Pro L655P. Login to comment 129 ABCD1 p.His667Leu H667L. Login to comment 130 ABCD1 p.His667Leu H667L. Login to comment 131 ABCD1 p.His667Leu DNA sequencing revealed the existence of a transversion c.2002A > T that leads to the missense mutation H667L. Login to comment 132 ABCD1 p.His667Leu DNA sequencing revealed the existence of a transversion c.2002A > T that leads to the missense mutation H667L. Login to comment 135 ABCD1 p.Gln574* Q574X. Login to comment 136 ABCD1 p.Gln574* Q574X. Login to comment 158 ABCD1 p.Gly266Arg ABCD1 p.Ser108Leu ABCD1 p.Arg591Trp While most of the missense mutations presented here may interfere with any of these processes, it is highly unlikely that this is the case for the S108L, G266R, and R591W missense mutations. Login to comment 159 ABCD1 p.Gly266Arg ABCD1 p.Ser108Leu ABCD1 p.Arg591Trp While most of the missense mutations presented here may interfere with any of these processes, it is highly unlikely that this is the case for the S108L, G266R, and R591W missense mutations. Login to comment