ABCMdb

PMID: 21300044

Lan F, Wang Z, Xie H, Huang L, Ke L, Yang B, Zhu Z
Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations.
Clin Chim Acta. 2011 May 12;412(11-12):970-4. Epub 2011 Feb 12., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCD1 p.Ser108* ABCD1 p.Lys602* ABCD1 p.Pro534Arg ABCD1 p.Arg280Leu ABCD1 p.Arg259Trp ABCD1 p.Ala314Pro ABCD1 p.Leu576Pro ABCD1 p.Gly343Val ABCD1 p.Asn148Asp ABCD1 p.His283Arg Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.P534R, p.fs A246, p.L576P, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89. Login to comment 6 ABCD1 p.His283Arg Three females from the same family developed AMN-like symptoms and they were heterozygous for the p.H283R mutation. Login to comment 52 ABCD1 p.Arg401Gln Of 19 missense mutations, 18 were distributed in the transmembrane domain (amino acid residues 51-350) or ATP binding domain (amino acid residues 501-651), only one mutation (p.R401Q) was located in the region between the above two domains, which is in accordance with previous notion that most missense mutations concentrated in transmembrane and ATP binding domains [10]. Login to comment 53 ABCD1 p.Ser108* ABCD1 p.Lys602* ABCD1 p.Pro534Arg ABCD1 p.Arg280Leu ABCD1 p.Arg259Trp ABCD1 p.Ala314Pro ABCD1 p.Leu576Pro ABCD1 p.Gly343Val ABCD1 p.Asn148Asp ABCD1 p.His283Arg Thirteen mutations were novel, i.e. p.R280L, p.P580L, p.G343V, p.S108X, p.R259W, p.fs A246, p.L576P, p.P534R, p.K602X, p.A314P, p.N148D, p.H283R, and p.fs R89, 9 of which were missense mutations. Login to comment 56 ABCD1 p.Ser108* ABCD1 p.Arg259Trp The mutations p.S108X and p.R259W occurred simultaneously in the same family and they lined tandemly on the same allele of ABCD1 gene, a phenomenon called multiple mutations. Login to comment 57 ABCD1 p.Lys217Glu Similar phenomenon was seen in pedigree 27, in which the mutation p.K217E co-existed tandem with a base change at codon V489 (1853GNA), without concomitant change of amino acid residue (p.V489V). Login to comment 59 ABCD1 p.Arg401Gln The mutation p.fs E471, or c.1415_1416delAG, was pinpointed in 3 families (1/10), p.R401Q was found in 2 families (1/15), and the rest were private. Login to comment 62 ABCD1 p.Leu576Pro The p.L576P mutation in pedigree 12 was not found in the maternal grandmother of the patient, but was found in his mother. Login to comment 82 ABCD1 p.Lys217Glu ABCD1 p.Ser108* ABCD1 p.Arg259Trp Two sets of multiple mutations, i.e. [p.S108X; p.R259W] and [p.K217E; p. V489V], were identified, which were new according to the international database (http://www.x-ald.nl), and it was the first time that multiple mutations were found in the ABCD1 gene in Chinese population. Login to comment 84 ABCD1 p.Arg401Gln ABCD1 p.Arg401Gln Only two mutations (p.fs E471 and p.R401Q) were shared by more than one families, with p.fs E471 being shared by 3 families (3/30, or 10%) and p.R401Q by 2 families (2/30, or 6.7%). Login to comment 93 ABCD1 p.His283Arg Considering the unsolved controversy over the mechanism of pathogenesis of female heterozygote patient [30], it might be hasty to correlate the mutation identified in this family (p.H283R) with the AMN phenotype, though there was a report demonstrating that a deletion mutation in ABCD1 gene might correlate with AMN [31]. Login to comment 99 ABCD1 p.Tyr174Cys ABCD1 p.Arg401Gln ABCD1 p.Arg401Gln ABCD1 p.Pro560Leu ABCD1 p.Gly512Ser ABCD1 p.Gln177* ABCD1 p.Gly266Arg ABCD1 p.Lys217Glu ABCD1 p.Arg617Cys ABCD1 p.Cys631Tyr ABCD1 p.Ser108* ABCD1 p.Ala141Thr ABCD1 p.Lys276Glu ABCD1 p.Arg617Gly ABCD1 p.Lys602* ABCD1 p.Pro534Arg ABCD1 p.Arg280Leu ABCD1 p.Arg259Trp ABCD1 p.Ala314Pro ABCD1 p.Leu576Pro ABCD1 p.Gly343Val ABCD1 p.Asn148Asp ABCD1 p.His283Arg ABCD1 p.Pro508Leu ABCD1 p.His283Asp Pedigree Number of patient Number of carriere Phenotype of patient Base change Amino acid change Position of mutation Feature of mutation Prenatal diagnosis 1 1 2 AdolCALD 1225GNT R280L Exon 1 Missense 2 1 1 CCALD 1909CNT P508L Exon 6 Missense 3 4 3 CCALD 1987CNG P534R Exon 6 Missense Y 4 1 1 CCALD 1182GNA G266R Exon 1 Missense 5 1a +1b 1 CCALD 2235CNG R617G Exon 8 Missense Y 6 1+1a +1c 1 CCALD 1414GNT G343V Exon 2 Missense 7 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift 8 1+1b 1 CCALD 2235CNT R617C Exon 8 Missense Yh 9 1 1 CCALD 2065CNT P560L Exon 7 Y 10 1+1a 2+1b CCALD [709 NA; 1161CNT] [S108X; R259W] Exon 1 Nonsense; Missense Y 11 1 1 CCALD 1126ins GCCATCG fs I246 Exon 1 Frameshift 12 1 1 CCALD 2113TNC L576P Exon 7 Missense 13 1a +2c 3 CCALD 807GNA A141T Exon 1 Missense 14 1 1 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 15 1 1+1b CCALD 915CNA Q177X Exon 1 Nonsense Yh 16 1+1a 1 CCALD 1588GNA R401Q Exon 3 Missense 17 1 1 CCALD 1212 ANG K276E Exon 1 Missense Y 18 1 1 CCALD 907 ANG Y174C Exon 1 Missense 19 1 2 CCALD 2190 ANT K602X Exon 8 Nonsense 20 1 1 CCALD 1326GNC A314P Exon 2 Missense 21 1 1 CCALD 828 ANG N148D Exon 1 Missense Y 22 1 1 CCALD 1588GNA R401Q Exon 3 Missense Y 23 1 0f CCALD 2278GNA C631Y Exon 9 Missense 24 1a 1 CCALD 1008insG fs S207 Exon 1 Frameshift Y 25 1 0f CCALD 1920GNA G512S Exon 6 Missense 26 1+1c 3 CCALD 1415_02 del AG fs E471 Exon 5 Frameshift Y 27 1+1b 1 CCALD [1035ANG; 1853GNA] [K217E; V489V] Exon 1 Missense; same sense Y 28 1+3d 4 AMNg 1234ANG H283R Exon 1 Missense 29 1+2a 3 CCALD 1233CNG H283D Exon 1 Missense 30 2 3 AMN; CCALD 656_57 delGA fs R89 Exon 1 Frameshift a patient or proband died at the time of referral; b fetus by prenatal diagnosis; c presymptomatic at the time of referral; d female heterozygote patient; e determined by molecular ananlysis or deduced by the fact that the carrier was the daughter of an X-ALD, or the mother of at least one X-ALD patients; f de novo mutation; g including three heterozygote female patients; h twice for two pregnancies. 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