ABCD1 p.Arg401Gly
| ClinVar: |
c.1201C>G
,
p.Arg401Gly
D
, Likely pathogenic
c.1202G>A , p.Arg401Gln D , Pathogenic |
| Predicted by SNAP2: | A: D (95%), 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%), S: D (95%), T: D (95%), 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, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Mutations, clinical findings and survival estimate... PLoS One. 2012;7(3):e34195. doi: 10.1371/journal.pone.0034195. Epub 2012 Mar 29. Pereira Fdos S, Matte U, Habekost CT, de Castilhos RM, El Husny AS, Lourenco CM, Vianna-Morgante AM, Giuliani L, Galera MF, Honjo R, Kim CA, Politei J, Vargas CR, Jardim LB
Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy.
PLoS One. 2012;7(3):e34195. doi: 10.1371/journal.pone.0034195. Epub 2012 Mar 29., [PMID:22479560]
Abstract [show]
In this study, we analyzed the ABCD1 gene in X-linked adrenoleukodystrophy (X-ALD) patients and relatives from 38 unrelated families from South America, as well as phenotypic proportions, survival estimates, and the potential effect of geographical origin in clinical characteristics. METHODS: X- ALD patients from Brazil, Argentina and Uruguay were invited to participate in molecular studies to determine their genetic status, characterize the mutations and improve the genetic counseling of their families. All samples were screened by SSCP analysis of PCR fragments, followed by automated DNA sequencing to establish the specific mutation in each family. Age at onset and at death, male phenotypes, genetic status of women, and the effect of family and of latitude of origin were also studied. RESULTS: We identified thirty-six different mutations (twelve novel). This population had an important allelic heterogeneity, as only p.Arg518Gln was repeatedly found (three families). Four cases carried de novo mutations. Intra-familiar phenotype variability was observed in all families. Out of 87 affected males identified, 65% had the cerebral phenotype (CALD). The mean (95% CI) ages at onset and at death of the CALD were 10.9 (9.1-12.7) and 24.7 (19.8-29.6) years. No association was found between phenotypic manifestations and latitude of origin. One index-case was a girl with CALD who carried an ABCD1 mutation, and had completely skewed X inactivation. CONCLUSIONS: This study extends the spectrum of mutations in X-ALD, confirms the high rates of de novo mutations and the absence of common mutations, and suggests a possible high frequency of cerebral forms in our population.
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No. Sentence Comment
55 NBF ND Northern Brazil 52/Male CALD p.Arg401Gly # E3 Missense c.1201C.G CGG.GGG - Inherited Southern Brazil 54/Female CALD p.Ser358fsX42 # E2 Frameshift+stop codon c.1074_1075insA Truncated TMD ND Northern Brazil 55/Female AMN p.Gly510Ser (http://www.x-ald.nl) E6 Missense c.1528G.A GGC.AGC NBF ND Northern Brazil 56/Male CALD p.Asp200Asn (Takano H et al., 1999) E1C Missense c.528G.A GAC.AAC TMD Inherited Northern Brazil 57/Male CALD p. Pro560Leu (Braun A et al., 1995) E7 Missense c.1679C.T CCG.CTG NBF Inherited Northern Brazil The number of family: the registration number in records of our lab. AMN: adrenomyeloneuropaty; AO: Addison only; #: new mutations identified in this study; NBF: nucleotide-binding fold; TMD: Transmembrane Domin; ND: not determined.
X
ABCD1 p.Arg401Gly 22479560:55:38
status: NEW90 The remaining four novel sequence variations (p.Pro623Leu, p.Leu628Glu, p.Ile481Phe and p.Arg401Gly), if not causative of the disease, were linked to X-ALD genotype by DNA study of hemizygous affected males.
X
ABCD1 p.Arg401Gly 22479560:90:90
status: NEW91 PolyPhen analysis of the four novel missense mutations considered three of them to be ''probably damaging`` p.Arg401Gly (PSIC score 3.071), p.Pro623Leu (PSIC score 3.379), and p.Leu628Glu (PSIC score 2.417), whereas p.Ile481Phe was considered ''benign`` Figure 1.
X
ABCD1 p.Arg401Gly 22479560:91:110
status: NEW