ABCMdb

PMID: 10369742

Perusi C, Gomez-Lira M, Mottes M, Pignatti PF, Bertini E, Cappa M, Vigliani MC, Schiffer D, Rizzuto N, Salviati A
Two novel missense mutations causing adrenoleukodystrophy in Italian patients.
Mol Cell Probes. 1999 Jun;13(3):179-82., [PubMed]

Sentences

No. Mutations Sentence Comment

3 ABCD1 p.Pro143Ser The first, a C813T transition, results in the substitution Pro143 Ser in the third putative transmembrane domain of the adrenoleukodystrophy protein (ALDP) in an adult onset case. Login to comment 4 ABCD1 p.Ser108Leu The second, a de novo C709T transition, results in a substitution Ser 108 Leu between the second and the third putative transmembrane segments, in a childhood case. Login to comment 21 ABCD1 p.Pro143Ser EX 1 219 181 81 Pro 143 Ser CTC CCT GCT * 0 G C C C T C T C T G C T A C C 1 (a) (b) {Fig. 1. Login to comment 22 ABCD1 p.Pro143Ser (a) Sequence determination of the C813T (Pro143Ser) mutation of the adrenoleukodystrophy (ALD)Patient 2. gene. Login to comment 40 ABCD1 p.Pro143Leu Since mutations C813T and C709T do not alter normally occurring restriction sites, we designed (Pro143Leu) (Fig. 1a). Login to comment 41 ABCD1 p.Pro143Ser ABCD1 p.Pro143Leu The mutation was confirmed Missense mutations in the ALD gene gene have been suggested to be around 8% or more.12,13 The mutation C813T results in a Pro 143 Ser substitution in the third putative transmembrane domain. Login to comment 42 ABCD1 p.Pro143Ser The mutation was confirmed Missense mutations in the ALD gene gene have been suggested to be around 8% or more.12,13 The mutation C813T results in a Pro 143 Ser substitution in the third putative transmembrane domain. Login to comment 43 ABCD1 p.Ser108Leu Moreover studies regarding a homologous peroxisomal transmembrane protein (PMP70) have suggested a role of the corresponding region for targeting and insertion in the peroxisomal membrane.14 The mutation C709T results in the substitution of serine 108 for leucine in the loop between the second and the third putative transmembrane segments. Login to comment 44 ABCD1 p.Ser108Trp ABCD1 p.Ser108Leu Other mutations in this segment have been described that cause ALD including the substitution of serine 108 for tryptophan described in a ChALD and in an AMN.9 The authors9 demonstrated that the substitution of this serine for tryptophan showed decreased ALDP immunoreactivity and a weak 75 kD ALDP band on Western blotting indicating that the substitution of serine 108 probably results in the synthesis of an unstable protein that is rapidly degraded in the cytosol. Login to comment 45 ABCD1 p.Ser108Trp Other mutations in this segment have been described that cause ALD including the substitution of serine 108 for tryptophan described in a ChALD and in an AMN.9 The authors9 demonstrated that the substitution of this serine for tryptophan showed decreased ALDP immunoreactivity and a weak 75 kD ALDP band on Western blotting indicating that the substitution of serine 108 probably results in the synthesis of an unstable protein that is rapidly degraded in the cytosol. Login to comment 46 ABCD1 p.Ser108Leu EX 1 96 77 Ser 108 Leu CTG TCG GTG * 0 C C T T C C T G T T G G T G A T (a) (b) T { Both amino acids involved in the substitutions de- Fig. 2. Login to comment 47 ABCD1 p.Ser108Leu ABCD1 p.Ser108Leu (a) Sequence determination of the C709T scribed here are conserved in mouse ALDP, mouse (Ser108Leu) mutation of the adrenoleukodystrophy (ALD) ALDRP and human ALDRP.15 Restriction analysisgene. Login to comment 48 ABCD1 p.Ser108Leu (a) Sequence determination of the C709T scribed here are conserved in mouse ALDP, mouse (Ser108Leu) mutation of the adrenoleukodystrophy (ALD) ALDRP and human ALDRP.15 Restriction analysis gene. Normal sequence is shown in the upper line. The demonstrated that the mutations were not present in * indicates the involved nucleotide. Login to comment 50 ABCD1 p.Pro143Ser ABCD1 p.Pro143Ser We there-analysis of the C709T mutation. After digestion of the 96 bp amplified product with Taq I, the normal allele fore conclude that mutations Pro143Ser and Ser- gives rise to two fragments of 77 and 19 bp, while the 108Leu are most likely to cause ALD in these two mutant allele presents only one band of 96 bp. Login to comment