ABCD1 p.Thr105Ile
| Predicted by SNAP2: | A: D (91%), C: D (95%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] X-linked adrenomyeloneuropathy associated with 14 ... Hum Genet. 1999 Jul-Aug;105(1-2):116-9. Wichers M, Kohler W, Brennemann W, Boese V, Sokolowski P, Bidlingmaier F, Ludwig M
X-linked adrenomyeloneuropathy associated with 14 novel ALD-gene mutations: no correlation between type of mutation and age of onset.
Hum Genet. 1999 Jul-Aug;105(1-2):116-9., [PMID:10480364]
Abstract [show]
Adrenomyeloneuropathy (AMN) represents a milder form of X-linked adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder. The disease is characterised by an abnormal accumulation of saturated, very long chain, fatty acids, because of altered peroxisomal beta-oxidation that concomitantly leads to demyelination in the central and peripheral nervous systems. ALD shows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect. Therefore, we have looked for a relationship between the molecular lesion and the age of onset in 19 patients with a well-classified clinical course of AMN. The nearly complete novel spectrum of ALD gene mutations identified has revealed no obvious correlation between the type of mutation and age of AMN onset in this small series. However, intrafamiliar concordance could be observed with respect to the occurrence of adrenocortical insufficiency. This supports the idea of one (or more) additional gene(s) contributing to the phenotypic expression of ALD.
Comments [show]
None has been submitted yet.
No. Sentence Comment
45 Mutations affecting amino acid residues T105 and R401 have been observed previously in patients with "Addison-only" symptoms (T105I; Feigenbaum et al. 1996) and childhood cerebral ALD or AMN (R401Q; Fuchs et al. 1994; Watkins et al. 1995; Krasemann et al. 1996), respectively, but, in these cases, are associated with different nucleotide substitutions.
X
ABCD1 p.Thr105Ile 10480364:45:126
status: NEW[hide] Mutational analysis and genotype-phenotype correla... Arch Neurol. 1999 Mar;56(3):295-300. Takano H, Koike R, Onodera O, Sasaki R, Tsuji S
Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.
Arch Neurol. 1999 Mar;56(3):295-300., [PMID:10190819]
Abstract [show]
BACKGROUND: X-linked adrenoleukodystrophy (ALD) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. The classic form of ALD usually has onset in childhood (childhood cerebral ALD), with rapid neurologic deterioration leading to a vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and Addison disease only also have been recognized. Despite discovery of the causative gene, a molecular basis for the diverse clinical presentations remains to be elucidated. OBJECTIVES: To conduct mutational analyses in 29 Japanese patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum of mutations in this gene, and to study genotype-phenotype correlations in Japanese patients. METHODS: The 29 patients comprised 13 patients with childhood cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated Japanese patients with ALD by genomic Southern blot analysis and direct nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction products derived from total RNA that was extracted from cultured skin fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes. RESULTS: Three patients with adult-onset cerebral ALD were identified as having large genomic rearrangements. The remaining 26 patients were identified as having 21 independent mutations, including 12 novel mutations resulting in small nucleotide alterations in the ALD gene. Eighteen (69%) of 26 mutations were missense mutations. Most missense mutations involved amino acids conserved in homologous gene products, including PMP70, mALDRP, and Pxa1p. The AG dinucleotide deletion at position 1081-1082, which has been reported previously to be the most common mutation in white patients (12%-17%), was also identified as the most common mutation in Japanese patients (12%). All phenotypes were associated with mutations resulting in protein truncation or subtle amino acid changes. There were no differences in phenotypic expressions between missense mutations involving conserved amino acids and those involving nonconserved amino acids. CONCLUSIONS: There are no obvious correlations between the phenotypes of patients with ALD and their genotypes, suggesting that other genetic or environmental factors modify the phenotypic expressions of ALD.
Comments [show]
None has been submitted yet.
No. Sentence Comment
87 Review of previous publications indicated that 14 missense mutations are associated exclu- sivelywithAMNorAddisondiseaseonly,includingC696T (R104C),33,34 G697A(R104H),42 C700T(T105I),45 G832A (S149N),35 C918G(Q178E),42 T1045C(L220P),35 C1137T (T254M),37 G1266A(A294T),45 C1551G(R389G),37 G1552A (R389H),33,35 C1638T (R418W),37 C1930T (S515F),38 T2084A(M566K),33 andG2211A(E606K).35,37 Analysisof these mutations may provide important insights into the mechanisms involved in variable phenotypic expressions in ALD.
X
ABCD1 p.Thr105Ile 10190819:87:176
status: NEW