ABCMdb

PMID: 26454440

Chu SS, Ye J, Zhang HW, Han LS, Qiu WJ, Gao XL, Gu XF
Eight novel mutations in the ABCD1 gene and clinical characteristics of 25 Chinese patients with X-linked adrenoleukodystrophy.
World J Pediatr. 2015 Nov;11(4):366-73. doi: 10.1007/s12519-015-0044-0. Epub 2015 Oct 11., [PubMed]

Sentences

No. Mutations Sentence Comment

86 ABCD1 p.Trp339Cys ABCD1 p.Gln178* ABCD1 p.Ile588His ABCD1 p.Cys476* ABCD1 p.Ser515Tyr Eight of the 22 mutations [c.1017G>T (p.W339C), c.892G>C (p.G289R), c.532C>T (p.Q178*), c.1544C>A (p.S515Y), c.1428C>A (p.C476*), c.1182delG (p.A395Lfs*15), c.424delC (p.L142Sfs*56), c.1759_1761dup (p.I588H)] were novel (Fig. 2). Login to comment 111 ABCD1 p.Arg401Gln ABCD1 p.Arg518Trp ABCD1 p.Tyr296Cys ABCD1 p.Arg617His ABCD1 p.Arg104Cys ABCD1 p.Arg104Cys ABCD1 p.Trp339Cys ABCD1 p.Ile588His ABCD1 p.Ser515Tyr ABCD1 p.Gly298Asp ABCD1 p.Ile474Thr ABCD1 p.Lys513Arg ABCD1 p.Leu325Pro ABCD1 p.Leu158Pro ABCD1 p.Gly298Arg However, some X-ALD males remain asymptomatic and one-third of heterozygous women remain free of clinical symptoms during their Patient number Exon Nucleotide change Amino acid change Protein localization References P1 2 c.1017G>T p.Trp339Cys TMD Novel P2 8 c.1850G>A p.Arg617His NBD Fanen et al, 1994[12] P4 1 c.892G>C p.Gly298Arg TMD Novel P5, P6 5 c.1415_16delAG p.Gln472Argfs*83 TMD to NBD Barcelo et al, 1994[13] P7 1 c.532C>T p.Gln178* TMD Novel P8 1 c.473T>C p.Leu158Pro TMD The peroxisomal diseases laboratory (unpublished) P10 6 c.1552C>T p.Arg518Trp NBD Fanen et al, 1994[12] P11 3 c.1202G>A p.Arg401Gln TMD to NBD Fuchs et al, 1994[14] P12 1 c.887A>G p.Tyr296Cys TMD Takano et al, 1999[15] P13 1 c.893G>A p.Gly298Asp TMD Lachtermacher et al, 2000[16] P14 1 c.310C>T p.Arg104Cys TMD Kok et al, 1995[17] P15 IVS 8 c.1866-10G>A p.Pro623fs* NBD Kemp et al, 1995[18] P16 5 c.1428C>A p.Cys476* NBD Novel P17 5 c.1421T>C p.Ile474Thr NBD Shimozawa et al, 2011[19] P18 6 c.1538A>G p.Lys513Arg NBD Piti&#e9;-Salp&#e9;tri&#e8;re Hospital (unpublished) P19 1 c.310C>T p.Arg104Cys TMD Kok et al, 1995[17] P20 6 c.1544C>A p.Ser515Tyr NBD Novel P21 2 c.901-1G>A p.Val301fs* TMD Kemp et al, 2001[20] P22 2 c.974T>C p.Leu325Pro TMD The peroxisomal diseases laboratory (unpublished) P23 3 c.1182delG p.Ala395Leufs*15 TMD to NBD Novel P24 1 c.424delC p.Leu142Serfs*56 TMD Novel P25 7 c.1759_1761dup p.Ile588His NBD Novel Table 2. Login to comment 114 ABCD1 p.Trp339Cys ABCD1 p.Ser515Tyr ABCD1 p.Gly298Arg Variables P1 P4 P20 cDNA mutations c.1017G>T c.892G>C c.1544C>A Protein level p.Trp339Cys p.Gly298Arg p.Ser515Tyr Conservation Highly conserved Highly conserved Highly conserved Polyphen prediction Probably damaging Probably damaging Probably damaging SIFT prediction Deleterious Deleterious Deleterious Align-GVGD Most likely to interfere with function Most likely to interfere with function Most likely to interfere with function Amino acid location (wild-type residue) A transmembrane domain ABC transmembrane type-1 ABC transporter Amino acid size change (than the wild-type residue) Smaller Bigger Bigger Amino acid physicochemical property change Aromatic amino acids to neutral polar amino acids (hydrophilicity) Non polar aliphatic amino acids to alkaline amino acids Neutral polar amino acids to aromatic amino acids (hydrophilic reduced) Charge characteristic change No Neutral to positive No Form a hydrogen bond with the neighbors No No Yes Influence from the mutant residue Disturb either the contacts with the other transmembrane domains or with the lipid-membrane Change the flexibility of wild-type residue which might abolish protein function The size difference makes that the new residue is not in the correct position and interferes with hydrogen bond Table 3. Login to comment 118 ABCD1 p.Trp339Cys ABCD1 p.Gln178* ABCD1 p.Ile588His ABCD1 p.Cys476* ABCD1 p.Ser515Tyr A: c.1017G>T (p.W339C); B: c.892G>C (p.G289R); C: c.532C>T (p.Q178*); D: c.1544C>A (p.S515Y); E: c.1428C>A (p.C476*); F: c.1182delG (p.A395Lfs*15); G: c.424delC (p.L142Sfs*56); H: c.1759_1761dup (p.I588H). Login to comment 121 ABCD1 p.Trp339Cys ABCD1 p.Ser515Tyr ABCD1 p.Gly298Arg b1;-Helix is presented in green, b2;-strands is displayed in yellow and coil is marked with gray respectively; B: Change of ALDP structure in three patients with novel missense mutations: c.1017G>T (p.Trp339Cys) in P1, c.892G>C (p.Gly298Arg) in P4, and c.1544C>A (p.Ser515Tyr) in P20. Login to comment 123 ABCD1 p.Trp339Cys ABCD1 p.Ser515Tyr ABCD1 p.Gly298Arg A B p.Trp339Cys p.Gly298Arg p.Ser515Tyr entire life. Login to comment