ABCMdb

ABCD1 p.Tyr174Ser

ClinVar:	c.520T>G , p.Tyr174Asp D , Pathogenic
Predicted by SNAP2:	A: D (91%), C: D (91%), D: D (95%), E: D (95%), F: D (85%), G: D (95%), H: D (91%), I: D (91%), K: D (95%), L: D (91%), M: D (95%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (95%), V: D (91%), W: 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, T: D, V: D, W: D,

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Publications
[hide] X-linked adrenoleukodystrophy in Spain. Identifica... Clin Genet. 2005 May;67(5):418-24. Coll MJ, Palau N, Camps C, Ruiz M, Pampols T, Giros M
X-linked adrenoleukodystrophy in Spain. Identification of 26 novel mutations in the ABCD1 gene in 80 patients. Improvement of genetic counseling in 162 relative females.
Clin Genet. 2005 May;67(5):418-24., [PMID:15811009]

Abstract [show]
In this study, we analyzed the ABCD1 gene in 80 X-linked adrenoleukodystrophy (X-ALD) patients from 62 unrelated families. We identified 53 different mutations, of which 26 are novel and two are non-pathogenic sequence variants (L516L and 3'UTR, 2246C/G) that have been previously described. The Spanish population had significant allelic heterogeneity, in which most of the mutations were exclusive to a single family 47/53 (88.7%). Only six mutations (Y174S, G277R, FsE471, R518Q, P543L, and R554H) were found in more than one family. Mutations G277R, P543L, and R554H were the most frequent, each of them being found in three patients (5%). Intra-familiar phenotype variability was observed in most of the families, but in one, with the novel mutation R120P, only the adult mild phenotype was present (five hemizygous family members). We detected 80 heterozygous women by mutation analysis, but only 78 of them showed increased very-long-chain fatty acid levels. In conclusion, this study extends the spectrum of mutations in X-ALD and facilitates the identification of heterozygous females. Our results are also consistent with previous studies reporting the difficulty of predicting genotype-phenotype correlation.

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No. Sentence Comment
6 Only six mutations (Y174S, G277R, FsE471, R518Q, P543L, and R554H) were found in more than one family. Login to comment
72 Only six mutations (Y174S, G277R, FsE471, R518Q, P543L, and R554H) have been found repeated in patients belonging to different families. Login to comment

[hide] Diffuse cortical hypometabolism on (18)F-FDG-PET s... Parkinsonism Relat Disord. 2012 Feb;18(2):210-2. Epub 2011 Sep 9. Kim JE, Choi KG, Jeong JH, Kang HJ, Kim HS
Diffuse cortical hypometabolism on (18)F-FDG-PET scan in a case of an adult variant cerebello-brainstem dominant form of ALD manifesting dementia.
Parkinsonism Relat Disord. 2012 Feb;18(2):210-2. Epub 2011 Sep 9., [PMID:21907609]

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23 The mutation of the c.521A > T (p.Tyr174Ser) of the ABCD1 gene in Xq28 was identified by direct sequencing of complementary DNA (cDNA). Login to comment

[hide] De novo missense mutation Y174S in exon 1 of the a... Hum Genet. 1995 Feb;95(2):235-7. Barcelo A, Giros M, Sarde CO, Pintos G, Mandel JL, Pampols T, Estivill X
De novo missense mutation Y174S in exon 1 of the adrenoleukodystrophy (ALD) gene.
Hum Genet. 1995 Feb;95(2):235-7., [PMID:7860075]

Abstract [show]
Adrenoleukodystrophy (ALD) is an X-linked disease, characterised by an alteration of the peroxisomal beta-oxidation of the very long chain fatty acids. The ALD gene has been identified and mutations have been detected in ALD patients. We report here a new missense mutation in the ALD gene of a male patient, predicting a tyrosine to serine substitution at codon 174 (mutation Y174S). The mother of the ALD patient does not have the Y174S mutation in her leukocyte DNA, indicating that Y174S arose de novo in the patient. Y174S is the first reported de novo mutation in the ALD gene.

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No. Sentence Comment
0 Hum Genet (1995) 95 :235-237 9 Springer-Verlag 1995 A. Barcel6 9M. Gir6s 9C. O. Sarde - G. Pintos J. L. Mandel 9T. P~tmpols 9X. Estivill De novo missense mutation Y174S in exon 1 of the adrenoleukodystrophy (ALD) gene Received: 26 July 1994 / Revised: 9 September 1994 Abstract Adrenoleukodystrophy (ALD) is an X-linked disease, characterised by an alteration of the peroxisomal [3-oxidation of the very long chain fatty acids. Login to comment
2 We report here a new missense mutation in the ALD gene of a male patient, predicting a tyrosine to serine substitution at codon 174 (mutation Y174S). Login to comment
3 The mother of the ALD patient does not have the Y174S mutation in her leukocyte DNA, indicating that Y174S arose de novo in the patient. Login to comment
4 Y174S is the first reported de novo mutation in the ALD gene. Login to comment
34 Based on a modification of the PCR-mediated mutagenesis system (Gregersen et al. 1991), the 120-bp product was shown to contain two newly-created RsaI restriction sites on normal alleles, but only one in the product from alleles harbouring the Y174S mutation. Login to comment
41 The change was an A to a C, predicting a protein with serine at residue 174 instead of tyrosine (mutation Y174S) (Fig. l a, b). Login to comment
43 Missense mutation Y174S occurred in a conserved region of the ALDP (Mosser et al. 1993) and was not found in 80 normal X chromosomes or in 10 unrelated ALD X chromosomes analysed by PCR-mediated mutagenesis. Login to comment
44 Fig.la-c Missense mutation Y174S in the ALD gene. Login to comment
49 c Analysis of mutation Y174S by PCR-mediated mutagenesis. Login to comment
52 After Rsal digestion, mutation Y174S leads to a fragment of 99bp and a small one of 21 bp. Login to comment
53 Normal individuals give a fragment of 80bp and two small ones of 19 and 21 bp that co-migrate We studied the mother and sister of patient MC by direct sequencing and by PCR-mediated mutagenesis (Fig. l c), and they were found not to have mutation Y174S in their leukocytes, The negative data for mutation Y174S in the mother and sister of patient MC agree with their normal VLCFA levels in serum and fibroblasts. Login to comment
55 These results confirm that Y174S is a de novo mutation. Login to comment
58 As far as we know, Y174S is the first de novo mutation reported in the ALD gene. Login to comment

[hide] X-linked adrenoleukodystrophy: are signs of hypogo... Hormones (Athens). 2014 Jan-Mar;13(1):146-52. Karapanou O, Vlassopoulou B, Tzanela M, Papadopoulos D, Angelidakis P, Michelakakis H, Ioannidis G, Mihalatos M, Kamakari S, Tsagarakis S
X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular failure?
Hormones (Athens). 2014 Jan-Mar;13(1):146-52., [PMID:24722136]

Abstract [show]
We present the clinical and hormonal findings of a young male with X-linked adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency since the age of 5 years, developed progressive neurological symptoms at the age of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty acids (VLCFAs) and genetic testing. His sexual body hair was sparse. Hormonal investigations revealed normal testosterone and inappropriately elevated LH levels. Androgen receptor gene analysis was negative for mutations or polymorphic variants associated with decreased receptor activity. Signs of hypogonadism in patients with confirmed X-ALD are not exclusively due to primary testicular failure. Tissue specific androgen resistance represents an alternative possibility. Since no loss-of-function mutations were detected in the androgen receptor, it is speculated that the patient's androgen resistance could be part of a functional defect mediated through VLCFA accumulation at the testosterone receptor and/or post-receptor levels.

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No. Sentence Comment
79 Different amino acid substitutions of the tyrosine 174 have been reported, namely, p.Tyr174His, p.Tyr174Asp, p.Tyr174Ser (www.x-ald. Login to comment