ABCMdb

PMID: 7849723

Fuchs S, Sarde CO, Wedemann H, Schwinger E, Mandel JL, Gal A
Missense mutations are frequent in the gene for X-chromosomal adrenoleukodystrophy (ALD).
Hum Mol Genet. 1994 Oct;3(10):1903-5., [PubMed]

Sentences

No. Mutations Sentence Comment

21 ABCD1 p.Gly266Arg G266R B 1 2 3 4 5 6 7 8 9 1O &* *•• m ~m m m - SB ~" ~ m Figure 1. Login to comment 27 ABCD1 p.Gly266Arg The band shift seen is due to the Gl 182A (G266R) mutation. Login to comment 31 ABCD1 p.Tyr174Asp * To whom correspondence should be addressed atUniversityofNorthCarolinaatChapelHillonMarch6,2012http://hmg.oxfordjournals.org/Downloadedfrom Human Molecular Genetics, 1994, Vol. 3, No. 10 /Ser--Mi mT^ - ~ - C *^ , ^ ^ -•»_ .. Y174D B 3'Asn148/Ser148 Ser 148 3 ' A C G T A C G T Phe G . Login to comment 35 ABCD1 p.Asn148Ser (A) Detection of A829G (N148S) in ALD exon 1. Login to comment 37 ABCD1 p.Gly266Arg (B) Detection of G1182A (G266R) in exon 1. Login to comment 39 ABCD1 p.Arg401Gln (C) Detection of G1588A (R401Q) in exon 3. Login to comment 42 ABCD1 p.Arg401Gln ABCD1 p.Gly266Arg ABCD1 p.Ser515Phe ABCD1 p.Arg418Trp Mutations identified in the ALD gene of 9 unrelated ALD patients/families Amino acid |Codon |Exon |ALDP-PMP70 | Restriction site Asnl48Ser Tyrl74Asp Gly266Arg Arg401Gln Arg418Trp Gln472-frameshift Glu477ter Ser515Phe AAC->AGC TAC->GAC GGG-»AGG CGG->CAG CGG->TGG delAG GAG-+TAG TCC-»TTC I I I III IV V V VI conserved conserved conserved conserved conserved conserved none +TaqI none none - Smal none none -Sad that are conserved between the ALD protein and PMP70. Login to comment 43 ABCD1 p.Arg401Gln ABCD1 p.Asn148Ser ABCD1 p.Gly266Arg ABCD1 p.Ser515Phe ABCD1 p.Arg418Trp ABCD1 p.Tyr174Asp These missense mutations are (positions of nucleotides and amino acids according to the ALD cDNA sequence in ref. 4) A829G (N148S), T906G (Y174D), Gl 182A (G266R), G1588A (R401Q), C1638T (R418W), and C1930T (S515F). Login to comment 44 ABCD1 p.Asn148Ser ABCD1 p.Gly266Arg ABCD1 p.Ser515Phe ABCD1 p.Tyr174Asp Co-segregation was confirmed between the disease phenotype and the mutations predicting Y174D, and S515F (Fig. 3), as well as for G266R (Fig. 1), and N148S (data not shown). Login to comment 45 ABCD1 p.Arg401Gln ABCD1 p.Ser515Phe ABCD1 p.Arg418Trp ABCD1 p.Arg418Trp For R401Q and R418W the families •e« M 1 2 3 4 5 B R418W C S515F r 1 2 3 4 5 6 M bp Figure 3. Identification of ALD mutations by restriction enzyme digestion. Login to comment 48 ABCD1 p.Tyr174Asp (A) The T906G transversion (Y174D) creates a TaqI site. Lane 1: undigested pattern of a control person. Login to comment 49 ABCD1 p.Arg418Trp (B) The C1638T transition (R418W) destroys a Smal site. Lane 1: DNA of unaffected control. Login to comment 50 ABCD1 p.Ser515Phe (C) Loss of a Sad site due to the C1930T transition (S515F). Login to comment 56 ABCD1 p.Ser515Phe In the case of the S515F mutation, as S515 is present in one of the ATP-binding folds which is entirely conserved between ALD and PMP70 (13), the amino acid substitution might well disturb the correct binding of ATP. Login to comment 59 ABCD1 p.Glu477* The two further mutations detected in this study should lead to significantly truncated ALD proteins; a G1815T transversion should result in a premature termination of translation at codon 477 (E477X), while a 2-bp deletion (del AG1801/1802) causes a frame shift from codon 472 which also results in termination of translation after the incorporation of additional 85 amino acids unrelated to the ALD protein. Login to comment 61 ABCD1 p.Glu477* In case of the E477X and delAG 1801/1802 mutations, the stability of the transcripts should be greatly reduced. Login to comment 64 ABCD1 p.Glu477* A silent G1934A substitution (L516L) was detected in the patient who carried the E477X mutation as well as in a further patient with an as yet unknown disease causing mutation. Login to comment