ABCD1 p.Thr632Pro
| 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%), R: D (95%), S: 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, R: D, S: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] X-linked adrenoleukodystrophy: ABCD1 de novo mutat... Mol Genet Metab. 2011 Sep-Oct;104(1-2):160-6. Epub 2011 Jun 22. Wang Y, Busin R, Reeves C, Bezman L, Raymond G, Toomer CJ, Watkins PA, Snowden A, Moser A, Naidu S, Bibat G, Hewson S, Tam K, Clarke JT, Charnas L, Stetten G, Karczeski B, Cutting G, Steinberg S
X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism.
Mol Genet Metab. 2011 Sep-Oct;104(1-2):160-6. Epub 2011 Jun 22., [PMID:21700483]
Abstract [show]
X-linked adrenoleukodystrophy (X-ALD) is a progressive peroxisomal disorder affecting adrenal glands, testes and myelin stability that is caused by mutations in the ABCD1 (NM_000033) gene. Males with X-ALD may be diagnosed by the demonstration of elevated very long chain fatty acid (VLCFA) levels in plasma. In contrast, only 80% of female carriers have elevated plasma VLCFA; therefore targeted mutation analysis is the most effective means for carrier detection. Amongst 489 X-ALD families tested at Kennedy Krieger Institute, we identified 20 cases in which the ABCD1 mutation was de novo in the index case, indicating that the mutation arose in the maternal germ line and supporting a new mutation rate of at least 4.1% for this group. In addition, we identified 10 cases in which a de novo mutation arose in the mother or the grandmother of the index case. In two of these cases studies indicated that the mothers were low level gonosomal mosaics. In a third case biochemical, molecular and pedigree analysis indicated the mother was a gonadal mosaic. To the best of our knowledge mosaicism has not been previously reported in X-ALD. In addition, we identified one pedigree in which the maternal grandfather was mosaic for the familial ABCD1 mutation. Less than 1% of our patient population had evidence of gonadal or gonosomal mosaicism, suggesting it is a rare occurrence for this gene and its associated disorders. However, the residual maternal risk for having additional ovum carrying the mutant allele identified in an index case that appears to have a de novo mutation is at least 13%.
Comments [show]
None has been submitted yet.
No. Sentence Comment
90 Previously reported (Yes/No) Number of pedigrees reporteda CpG (Yes/No) 25 c.124delC ND No 1 N/A 5 c.279_280ins12bp (p.Leu93_Leu94insGluThrGlyLeu) ND No 1 No 6 c.410G>A (p.Trp137X) ND No 1 No 7 c.412_414delCTC (p.Leu139del) ND Yes 2 No 26 c.476del24 ND No 1 N/A 4 c.593C>G (p.Thr198Met) N/A No 1 Yes 8 c.695_696insG (p.Ala233fsX67) ND No 1 Yes 2 c.725G>A (p.Trp242X) Gonosomal No 1 No c.796G>A (p.Gly266Arg) ND Yes 23 Yes 27 c.797G>A (p.Gly266Gln) ND No 1 No 12 c.944C>A (p.Ser315X) ND No 1 Yes 13 c.1201C>T (p.Arg401Trp) ND Yes 12 Yes 14 c.1225-2A>G (splice defect) ND No 1 No 15 c.1390C>T (p.Arg464X) ND Yes 11 Yes 16 c.1553G>A (p.Arg518 Gln) ND Yes 20 Yes 17 c.1567C>T (p.Leu523Phe) ND No 1 No 18 c.1609C>T (p.Gln537X) ND No 1 No 28 c.1619T>G (p.Phe540Cys) ND No 1 No 19 c.1679C>T (p.Pro560Leu) ND Yes 20 Yes 29 c.1679C>T (p.Pro560Leu) ND Yes 20 Yes 20 exon3 to exon10 deletion ND Yesb 9 N/A 30 c.1781-1G>A ND No 1 No 21 c.1816T>C (p.Ser606Pro) ND Yes 3 No 31 c.1850G>A (p.Arg617His) ND Yes 20 Yes 22 c.1876G>A (p.Ala626Thr) ND Yes 10 Yes 23 c.1894A>C (p.Thr632Pro) ND No 2 No 1 c.1899C>A (p.Ser633Arg) Gonosomal Yes 2 Yes 24 c.1918 G>A (p.Glu640Lys) ND No 2 No 3 c.2030G>A (p.Gly677Asp) Gonadal No 1 Yes de novo mutation in male index case with childhood cerebral X-ALD;somatic and/or gonadal mosaicisim; de novo mutationND = none detected; N/A = not applicable; Color codes: in female carrier.
X
ABCD1 p.Thr632Pro 21700483:90:1058
status: NEW[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.
Comments [show]
None has been submitted yet.
No. Sentence Comment
26 NBF Inherited Northern Brazil 31/Male CALD p.Arg518Gln (Imamura A et al., 1997) E6 Missense c.1553G.A CGG.CAG NBF de novo Southern Brazil 32/Male CALD p.Arg401Trp (Takano H et al., 1999) E3 Missense c.1201C.T CGG.UGG - ND Southern Brazil 33/Male CALD p.Thr632Pro (http://www.x-ald.nl) E9 Missense c.1894A.C ACC.CCC NBF de novo Southern Brazil 36/Male CALD p.Arg518Gln (Imamura A et al., 1997) E6 Missense c.1553G.A CGG.CAG NBF Inherited Northern Brazil 37/Male CALD p.Ser358X (Coll MJ et al., 2005) E2 Stop codon c.1073C.G UCA.UGA TMD Inherited Southern Brazil 38/Male CALD p.Ile481Phe # E5 Missense c.1441A.T AUC.UUC NBF Inherited Northern Brazil 39/Male AMN p.Arg389Gly (Krasemann EW et al., 1996) E3 Missense c.1165C.G CGC.GGC - ND Argentina 40/Male AMN p.Gln472fsX83 (Barcelo &#b4; A et al., 1994) E5 Frameshift+stop codon c.1415_1416delAG Truncated - Inherited Uruguay 41/Male CALD p.Ala95fsX11 # E1B Frameshift+stop codon c.283_284ins9 Elonged TMD Inherited Southern Brazil 44/Male CALD p.Ser606Pro (Feigenbaum V et al. 1996) E8 Missense c.1816T.C UCG.CCG NBF Inherited Northern Brazil 45/Male CALD p.Gln55X # E1A Stop codon c.163C.T Truncated - Inherited Northern Brazil 46/Male CALD p.Glu199Lys (http://www.x-ald.nl) E1C Missense c.595G.A GAG.AAG TMD ND Northern Brazil common central demyelinative disease.
X
ABCD1 p.Thr632Pro 22479560:26:253
status: NEW[hide] Clinical, biochemical, neuroimaging and molecular ... Metab Brain Dis. 2015 Dec;30(6):1439-44. doi: 10.1007/s11011-015-9717-6. Epub 2015 Aug 12. Jiang MY, Cai YN, Liang CL, Peng MZ, Sheng HY, Fan LP, Lin RZ, Jiang H, Huang Y, Liu L
Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China.
Metab Brain Dis. 2015 Dec;30(6):1439-44. doi: 10.1007/s11011-015-9717-6. Epub 2015 Aug 12., [PMID:26260157]
Abstract [show]
X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism. Mutation c.1180delG was demonstrated to be de novo mutation. 26.3 % (5/19) patients carried the deletion c.1415_16delAG, which may be the mutational hot spot in South China population. In addition, 73.7 % (14/19) patients were type of childhood cerebral adrenoleukodystrophy, 26.3 %(5/19) were in Addison only. Half of the childhood cerebral adrenoleukodystrophy patients had the adrenocortical insufficiency preceded the onset of neurological symptoms. Furthermore, 5 of 19 cases underwent hematopoietic stem cell transplantation. Our data showed that hematopoietic stem cell transplantation performed at an advanced stage of the cerebral X- linked adrenoleukodystrophy would accelerate the progression of the disease. Good clinical outcome achieved when hematopoietic stem cell transplantation performed at the very early stage of the disease.
Comments [show]
None has been submitted yet.
No. Sentence Comment
74 Reference range Table 1 ABCD1 mutations and phenotypes of 19 X-linked adrenoleukodystrophy male patients Patient Exon Nucleotide change Amino acid change Phenotype 1 1 c.102_103insCa p.Leu35LeufsX159a AO 2 1 c.347_348delGAinsATa p.Gly116Aspa CCALD 3 1 c.521A>G p.Tyr174Cys CCALD 4 1 c.785C>Aa p.Ser262Xa CCALD 5 2 c.982G>Ta p.Val328Phea AO 6 3 c.1109 T>Aa p.Leu370xa CCALD 7 3 c.1180delGab p.Ala394ArgfsX15a CCALD 8 3 c.1180delGab p.Ala394ArgfsX15a CCALD 9 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 10 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 11 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 12 5 c.1415_16delAG p.Gln472Argfs*83 AO 13 5 c.1415_16delAG p.Gln472Argfs*83 CCALD 14 6 c.1553G>A; c.1548G>A p.Arg518Gln; p.Leu516Leu CCALD 15 7 c.1661G>A p.Arg554His CCALD 16 7 c.1724_1725insCa p.Leu576ProfsX24a AO 17 9 c.1894A>C p.Thr632Pro CCALD 18 - IVS2_IVS5del - CCALD 19 - IVS2_IVS5del - AO a Novel mutation b De novo mutation have been identified in the ABCD1 gene, in which 695 (44 %) mutations appear to be non-recurrent.
X
ABCD1 p.Thr632Pro 26260157:74:816
status: NEW