title: ABCB6 (MTABC3) excluded as the causative gene for the growth retardation syndrome with aminoaciduria, cholestasis, iron overload, and lactacidosis.
abstract: GRACILE syndrome (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death; OMIM 603358) is a rare metabolic disorder with autosomal recessive mode of inheritance. So far it has been diagnosed only in patients with Finnish ancestors. The GRACILE locus has been positioned to a restricted region of chromosome 2q33-37, but the causative gene remains to be identified. The ABCB6 gene, involved in iron homeostasis, mitochondrial respiratory function, and maintenance of the stability of mitochondrial DNA, has been positioned to this same chromosomal region, and advocated in literature as a highly probable candidate gene for the syndrome on both functional and positional grounds. We carried out sequence and quantitative expression analyses to detect potential disease-associated mutations in the ABCB6 gene. No mutations in the coding region of ABCB6 were found, and the expression level of ABCB6 in patient fibroblasts was found to be comparable to controls. Haplotype analysis of the critical DNA region provided evidence for positional exclusion also. Based on these data, ABCB6 is not the causative gene for GRACILE syndrome.
authors.affiliation: Department of Human Genetics, UCLA School of Medicine, Los Angeles, California, USA. ilona.visapaa@ktl.fi
authors.forename: Ilona
authors.initials: I
authors.lastname: Visapää
authors.forename: Vineta
authors.initials: V
authors.lastname: Fellman
authors.forename: Lisa
authors.initials: L
authors.lastname: Lanyi
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000140:Acidosis, Lactic / Q000473:pathology; D015152:Blotting, Northern; D002779:Cholestasis / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006130:Growth Disorders / Q000473:pathology*; D006239:Haplotypes; D006801:Humans; D007501:Iron / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000608:Renal Aminoacidurias / Q000473:pathology*; D013577:Syndrome
chemical_list: C107991:ABCB6 protein, human; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D004247:DNA; D007501:Iron