ABCD1 p.Arg660Gln
| 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] Molecular analysis of ABCD1 gene in Indian patient... Clin Chim Acta. 2011 Nov 20;412(23-24):2289-95. Epub 2011 Aug 26. Shukla P, Gupta N, Gulati S, Ghosh M, Vasisht S, Sharma R, Gupta AK, Kalra V, Kabra M
Molecular analysis of ABCD1 gene in Indian patients with X-linked adrenoleukodystrophy.
Clin Chim Acta. 2011 Nov 20;412(23-24):2289-95. Epub 2011 Aug 26., [PMID:21889498]
Abstract [show]
BACKGROUND: X-linked Adrenoleukodystrophy (X-ALD), with an incidence of 1:14,000 is the most frequent monogenic demyelinating disorder worldwide. The principal biochemical abnormality in X-ALD is the increased levels of saturated, unbranched very long chain fatty acids (VLCFA). It is caused by mutations in ABCD1 gene. No molecular data on X-ALD is available in India and mutational spectrum in Indian patients is not known. METHODS: We standardized conformation sensitive gel electrophoresis (CSGE) method to detect mutations in ABCD1 gene in twenty Indian patients with X-ALD. The results were confirmed by sequencing. Genotype-phenotype correlation was also attempted. Prenatal diagnosis (PND) in one family was done using chorionic villi (CV) sample at 12 weeks of gestation. RESULTS: Out of twenty, causative mutations could be identified in twelve patients (60%). Six reported and four novel mutations were identified. Three polymorphisms were also observed. No hot spot was found. No significant genotype-phenotype correlation could be established. CONCLUSIONS: The study identified the mutation spectrum of Indian X-ALD patients, which enabled us to offer accurate genetic counseling, carrier detection and prenatal diagnosis where needed.
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No. Sentence Comment
68 Six reported mutations, c.1202 GNA (p.Arg401Gln), c.1679 CNT (p.Pro560Leu), c.1816 TNC (p.Ser606Pro), 1547 TNC (p. Leu516Pro), c.1780+2 TNG (p.Gly593fs), c.1979 GNA (p.Arg660Gln) were found in eight patients (Fig. 1a, b, c and d).
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ABCD1 p.Arg660Gln 21889498:68:168
status: NEW69 All mutations were unique except two, c.1679 CNT (p.Pro560Leu) and c.1979 GNA (p. Arg660Gln) which were found in two unrelated families.
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ABCD1 p.Arg660Gln 21889498:69:82
status: NEW73 Data analysis Results of data analysis done by PolyPhen tool for the missense mutations found in X-ALD patients showed all missense changes, c.1202 GNA (p.Arg401Gln), c.1679 CNT (p.Pro560Leu), c.1816 TNC (p.Ser606Pro), c.1547 TNC (p.Leu516Pro) c.1979 GNA (p.Arg660Gln) as probably damaging (Table 3).
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ABCD1 p.Arg660Gln 21889498:73:258
status: NEW110 The mutation, c.1979 GNA (p.Arg660Gln) was found in exon 9 in two patients (A16 and A18), along with two other synonymous changes, p.Ala650Ala, and p.Ser633Ser in both patients.
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ABCD1 p.Arg660Gln 21889498:110:28
status: NEW124 CCER No A5b 34 39 Neuroregression, behavior problem, speech problem, abnormal gait, urinary incontinence AMN c.1679 CNT (p.Pro560Leu) in exon7/c.420 CNA (p.Ile140Ile) (unreported) in exon 1 A6 13 15 Hyperactivity, slurred speech, spastic gait, deterioration of vision AMN No A7b 22 26 Neuroregression, deterioration of vision, cognitive decline, aggressive behavior, spastic gait, urinary incontinence Adult Cerebral c.1938_1939dupGG (p.Ala647fs) in exon 9 A8 4 4.5 Deterioration of vision and hearing, delayed micturition CCER No A9 6 6 Neuroregression, deterioration of vision and hearing, behavior problem, slurred speech, abnormal gait CCER c.1816 TNC (p.Ser606Pro) in exon 8 2.499 Probably damaging A10b 8 8 Neroregression, deterioration of vision, cognitive decline, speech problem, spastic gait CCER c.1394-2ANG in intron 4 A11 15 22 Neuroregression, seizures, deterioration of vision, cognitive decline, speech problem, spastic gait Adolescent c.67_83del17 (p.Ala23fs) in exon 1 A12b 20 21 Neuroregression, speech problem, abnormal gait, urinary incontinence AMN c.1547 TNC (p.Leu516Pro) in exon 6 2.482 Probably damaging A13 45.5 46 Neuroregression, spastic paraparesis, deterioration of vision and hearing, memory decine, behavior problem, cognitive decline, impotence, urinary incontinence Adult cerebral c.1780+2 TNG in exon 7 A14 11 11 Neuroregression, deterioration of hearing, deterioration of school performance, behavior problem, gait abnormaility Adolescent No A15 9 12 Loss of vision and hearing, low volume speech CCER c.395 GNA (p.Trp132X) in exon 1 A16 1 14 Neuroregression, seizures, deterioration of school performance, behavioral problem CCER c.1979 GNA (p.Arg660Gln) in exon 9/p.Ala650Ala, p. Ser633Ser in exon 9 2.409 Probably damaging A17b 0.3 9 Seizures, weakness of right limbs, speech problem, abnormal gait CCER No A18 0.9 15 Neuroregression, deterioration of vision and hearing, behavioral problem, cognitive decline, speech problem, abnormal gait CCER c.1979 GNA (p.Arg660Gln) in exon 9/p.Ala650Ala, p. Ser633Ser in exon 9 2.409 Probably damaging A19 0.6 14 Loss of vision and hearing, speech problem CCER No/p.Ser633Ser in exon 9 A20 12 14 Spastic quadriparaparesis, mild cognitive decline, delayed puberty AMN No CCER: Childhood Cerebral.
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ABCD1 p.Arg660Gln 21889498:124:1682
status: NEWX
ABCD1 p.Arg660Gln 21889498:124:2000
status: NEW142 Most of the mutations found in our study were unique to the kindreds except two missense mutations, c.1679 CNT (p.Pro560Leu) in exon 7 (found A3 and A5) and c.1979 GNA (p.Arg660Gln) in exon 9 (found in A16 and A18) of the ABCD1 gene.
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ABCD1 p.Arg660Gln 21889498:142:171
status: NEW166 This phenotype was found in patients with splice site mutation, insertion and nonsense mutation as well as patients having missense mutations, c.1202 GNA (p.Arg401Gln), c.1816 TNC (p.Ser606Pro) and c.1979 GNA (p.Arg660Gln) (Table 4).
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ABCD1 p.Arg660Gln 21889498:166:212
status: NEW[hide] Genomic profiling identifies novel mutations and S... PLoS One. 2011;6(9):e25094. Epub 2011 Sep 22. Kumar N, Taneja KK, Kalra V, Behari M, Aneja S, Bansal SK
Genomic profiling identifies novel mutations and SNPs in ABCD1 gene: a molecular, biochemical and clinical analysis of X-ALD cases in India.
PLoS One. 2011;6(9):e25094. Epub 2011 Sep 22., [PMID:21966424]
Abstract [show]
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD.
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No. Sentence Comment
87 The lower left panel shows the four novel mutations (a) c.1903_04insCCA/ Val635delinsAlaMet (TGG in antisense strand with reverse primer), (b) c.1979G.A/Arg660Gln, (c) c.1993_95delinsGAG/Lys665delinsGlu and (d) c.1673T.C/Ile558Thr.
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ABCD1 p.Arg660Gln 21966424:87:153
status: NEW105 The 2 missense novel mutations c.1673T.C (Ile558Thr) and c.1979G.A (Arg660Gln) were identified in exons 7 and 9 respectively.
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ABCD1 p.Arg660Gln 21966424:105:68
status: NEW156 Patients Phenotype1 Age(Year) Sex Exon/IVS Mutation Type Mutations Protein Localization ALDP PSIC Score5 P01* ccALD 4 M 9 Inframe del/ins c.1903_04delinsCCA/Val635delinsAlaMet NBF + + - P02* ccALD 5 M 9 Missense c.1979G.A/Arg660Gln - - 2.409 P03 ccALD 3 M IVS84 Frameshift g.1866-10G.A/Arg622fs Walker B3 - - P04 ccALD 4.5 M 1 Missense c.796G.A/Gly266Arg TMD + ++ 2.539 P05 ccALD 6 M 9 Frameshift c.1939_40insGG/Ala646fs NBF n.d - P06 ccALD 7 M 2 Missense c.904G.A/Glu302Lys TMD + + 2.194 P07 ccALD 8 M 3 Missense c.1202G.A/Arg401Gln - + ++ 2.396 P08* ccALD 8 M 10 Inframe del/ins c.1993_95delinsGAG/Lys665delinsGlu - + + - P09 AdolCALD 11 M 1 Missense c.796G.A/Gly266Arg TMD + ++ 2.539 P10 AdolCALD 11 M 8 Missense c.1816T.C/Ser606Pro C sequence - 2.499 P11 AdolCALD 15 M IVS8 Frameshift g.1866-10G.A/Arg622fs Walker B + - P12 ACALD 42 M 8 Missense c.1825G.A/Glu609Lys C sequence3 - 2.075 P13* ACALD 46 M 7 Missense c.1673T.C/Ile558Thr NBF3 + ++ 1.211 P14 AMN 26 M 9 Frameshift c.1939_40insGG/Ala646fs - - - P15 AMN 35 M 1 Missense c.796G.A/Gly266Arg TMD2 + ++ 2.539 P16 Asymptomatic 18 F 7 Missense c.1771C.T/Arg591Trp NBF + ++ 2.818 P17 Asymptomatic 26 F 1 Frameshift c.110_17del8/Val36fs - + + - *Novel Mutations, 1 ccALD-Childhood Adrenoleukodystrophy, AMN-Adrenomyeloneuropathy, ACALD-Adult Cerebral Adrenoleukodystrophy, AdolCALD- Adolescent cerebral Adrenoleukodystrophy.
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ABCD1 p.Arg660Gln 21966424:156:222
status: NEW168 Lane 1 and 10 (Control by symbol ''C``), Lane 2 (P01, ccALD, V635delins A & M), Lane 3 (P02, ccALD, R660Q), Lane 4 (P03, ccALD, R622fs), Lane 5 (P04, ccALD, G266R), Lane 6 (P06, ccALD, E302K), Lane 7 (P07, ccALD, R401Q), Lane 8 (P08, ccALD, K665delinsE), Lane 9 (P09, AdolCALD, G266R), Lane 11 (P10, AdolCALD, S606P), Lane 12 (P11, AdolCALD, R622fs), Lane 13 (P12, ACALD, E609K), Lane 14 (P13, ACALD, I558T), Lane 15 (P14, AMN, A646fs), Lane 16 (P15, AMN, G266R), Lane 17 (P16, asymptomatic female, R591W) and Lane 18 (P17, asymptomatic female,).
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ABCD1 p.Arg660Gln 21966424:168:100
status: NEW86 The lower left panel shows the four novel mutations (a) c.1903_04insCCA/ Val635delinsAlaMet (TGG in antisense strand with reverse primer), (b) c.1979G.A/Arg660Gln, (c) c.1993_95delinsGAG/Lys665delinsGlu and (d) c.1673T.C/Ile558Thr.
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ABCD1 p.Arg660Gln 21966424:86:153
status: NEW104 The 2 missense novel mutations c.1673T.C (Ile558Thr) and c.1979G.A (Arg660Gln) were identified in exons 7 and 9 respectively.
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ABCD1 p.Arg660Gln 21966424:104:68
status: NEW155 Patients Phenotype1 Age(Year) Sex Exon/IVS Mutation Type Mutations Protein Localization ALDP PSIC Score5 P01* ccALD 4 M 9 Inframe del/ins c.1903_04delinsCCA/Val635delinsAlaMet NBF + + - P02* ccALD 5 M 9 Missense c.1979G.A/Arg660Gln - - 2.409 P03 ccALD 3 M IVS84 Frameshift g.1866-10G.A/Arg622fs Walker B3 - - P04 ccALD 4.5 M 1 Missense c.796G.A/Gly266Arg TMD + ++ 2.539 P05 ccALD 6 M 9 Frameshift c.1939_40insGG/Ala646fs NBF n.d - P06 ccALD 7 M 2 Missense c.904G.A/Glu302Lys TMD + + 2.194 P07 ccALD 8 M 3 Missense c.1202G.A/Arg401Gln - + ++ 2.396 P08* ccALD 8 M 10 Inframe del/ins c.1993_95delinsGAG/Lys665delinsGlu - + + - P09 AdolCALD 11 M 1 Missense c.796G.A/Gly266Arg TMD + ++ 2.539 P10 AdolCALD 11 M 8 Missense c.1816T.C/Ser606Pro C sequence - 2.499 P11 AdolCALD 15 M IVS8 Frameshift g.1866-10G.A/Arg622fs Walker B + - P12 ACALD 42 M 8 Missense c.1825G.A/Glu609Lys C sequence3 - 2.075 P13* ACALD 46 M 7 Missense c.1673T.C/Ile558Thr NBF3 + ++ 1.211 P14 AMN 26 M 9 Frameshift c.1939_40insGG/Ala646fs - - - P15 AMN 35 M 1 Missense c.796G.A/Gly266Arg TMD2 + ++ 2.539 P16 Asymptomatic 18 F 7 Missense c.1771C.T/Arg591Trp NBF + ++ 2.818 P17 Asymptomatic 26 F 1 Frameshift c.110_17del8/Val36fs - + + - *Novel Mutations, 1 ccALD-Childhood Adrenoleukodystrophy, AMN-Adrenomyeloneuropathy, ACALD-Adult Cerebral Adrenoleukodystrophy, AdolCALD- Adolescent cerebral Adrenoleukodystrophy.
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ABCD1 p.Arg660Gln 21966424:155:222
status: NEW167 Lane 1 and 10 (Control by symbol ''C``), Lane 2 (P01, ccALD, V635delins A & M), Lane 3 (P02, ccALD, R660Q), Lane 4 (P03, ccALD, R622fs), Lane 5 (P04, ccALD, G266R), Lane 6 (P06, ccALD, E302K), Lane 7 (P07, ccALD, R401Q), Lane 8 (P08, ccALD, K665delinsE), Lane 9 (P09, AdolCALD, G266R), Lane 11 (P10, AdolCALD, S606P), Lane 12 (P11, AdolCALD, R622fs), Lane 13 (P12, ACALD, E609K), Lane 14 (P13, ACALD, I558T), Lane 15 (P14, AMN, A646fs), Lane 16 (P15, AMN, G266R), Lane 17 (P16, asymptomatic female, R591W) and Lane 18 (P17, asymptomatic female,).
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ABCD1 p.Arg660Gln 21966424:167:100
status: NEW