ABCMdb

PMID: 21966424

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., [PubMed]

Sentences

No. Mutations Sentence Comment

86 ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr 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. Login to comment 87 ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr 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. Login to comment 100 ABCD1 p.Gly266Arg One common recurrent missense mutation c.796G.A (Gly266Arg) in exon 1 was present in three patients from unrelated families with different phenotypes. Login to comment 101 ABCD1 p.Gly266Arg One common recurrent missense mutation c.796G.A (Gly266Arg) in exon 1 was present in three patients from unrelated families with different phenotypes. Login to comment 102 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Glu302Lys Of the 10 non-recurrent mutations in our study group i.e a frameshift mutation c.110_117del8 (Val36fs) in exon 1 was identified in an asymptomatic heterozygous female and 5 missense mutations, c.904G.A (Glu302Lys) in exon 2, c.1202G.A (Arg401Gln) in exon 3, c.1771C.T (Arg591Trp) in exon 7, c.1816T.C (Ser606Pro) and c.1825G.A (Glu609Lys) in exon 8 were present in 5 different patients. Login to comment 103 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Glu302Lys Of the 10 non-recurrent mutations in our study group i.e a frameshift mutation c.110_117del8 (Val36fs) in exon 1 was identified in an asymptomatic heterozygous female and 5 missense mutations, c.904G.A (Glu302Lys) in exon 2, c.1202G.A (Arg401Gln) in exon 3, c.1771C.T (Arg591Trp) in exon 7, c.1816T.C (Ser606Pro) and c.1825G.A (Glu609Lys) in exon 8 were present in 5 different patients. Login to comment 104 ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr The 2 missense novel mutations c.1673T.C (Ile558Thr) and c.1979G.A (Arg660Gln) were identified in exons 7 and 9 respectively. Login to comment 105 ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr The 2 missense novel mutations c.1673T.C (Ile558Thr) and c.1979G.A (Arg660Gln) were identified in exons 7 and 9 respectively. Login to comment 155 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr ABCD1 p.Glu302Lys 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. Login to comment 156 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr ABCD1 p.Glu302Lys 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. Login to comment 167 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr ABCD1 p.Glu302Lys 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,). Login to comment 168 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Arg660Gln ABCD1 p.Ile558Thr ABCD1 p.Glu302Lys 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,). Login to comment 176 ABCD1 p.Gly266Arg Thus, a definite hot-spot mutation in Indian patients could not be observed, although c.796G.A (Gly266Arg) mutation in the transmembrane domain in exon 1 was present in three unrelated patients of different phenotypes. Login to comment 177 ABCD1 p.Gly266Arg ABCD1 p.Gly266Arg Thus, a definite hot-spot mutation in Indian patients could not be observed, although c.796G.A (Gly266Arg) mutation in the transmembrane domain in exon 1 was present in three unrelated patients of different phenotypes. Login to comment 178 ABCD1 p.Gly266Arg Interestingly, a novel intronic SNP 1992-32C/T was also observed in IVS9 in the patient with ccALD phenotype possessing c.796G.A (Gly266Arg). Login to comment 197 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Glu302Lys Supporting Information Supporting Information S1 Frequently occurring mutations in (a) intervening sequence 8 (g.1866-10G.A/Arg622fs, shown as C.T in antisense strand) in P03 and P11, (b) exon 1 (c.796G.A/ Gly266Arg, shown as C.T in antisense strand) in P04, P09 and P15, (c) exon 9 (c.1939_40insGG/Ala646fs, shown as CC in antisense strand) in P05 and P14, (d) exon 2 (c.904G.A/ Glu302Lys) in P06, (e) exon 3 (c.1202G.A/Arg401Gln) in P07, (f) exon 8 (c.1816T.C/Ser606Pro) in P10, (g) exon 8 (c.1825G.A/ Glu609Lys) in P12, (h) exon 7 (c.1771C.T/Arg591Trp) in P16 and (i) exon 1 (c.110_17del8/Val36fs) in P17. Login to comment 198 ABCD1 p.Arg401Gln ABCD1 p.Ser606Pro ABCD1 p.Gly266Arg ABCD1 p.Glu609Lys ABCD1 p.Arg591Trp ABCD1 p.Glu302Lys Supporting Information Supporting Information S1 Frequently occurring mutations in (a) intervening sequence 8 (g.1866-10G.A/Arg622fs, shown as C.T in antisense strand) in P03 and P11, (b) exon 1 (c.796G.A/ Gly266Arg, shown as C.T in antisense strand) in P04, P09 and P15, (c) exon 9 (c.1939_40insGG/Ala646fs, shown as CC in antisense strand) in P05 and P14, (d) exon 2 (c.904G.A/ Glu302Lys) in P06, (e) exon 3 (c.1202G.A/Arg401Gln) in P07, (f) exon 8 (c.1816T.C/Ser606Pro) in P10, (g) exon 8 (c.1825G.A/ Glu609Lys) in P12, (h) exon 7 (c.1771C.T/Arg591Trp) in P16 and (i) exon 1 (c.110_17del8/Val36fs) in P17. Login to comment