title: Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1.
abstract: The BCAP31 gene is located between SLC6A8, associated with X-linked creatine transporter deficiency, and ABCD1, associated with X-linked adrenoleukodystrophy. Recently, loss-of-function mutations in BCAP31 were reported in association with severe developmental delay, deafness and dystonia. We characterized the break points in eight patients with deletions of SLC6A8, BCAP31 and/or ABCD1 and studied the genotype-phenotype correlations. The phenotype in patients with contiguous gene deletions involving BCAP31 overlaps with the phenotype of isolated BCAP31 deficiency. Only deletions involving both BCAP31 and ABCD1 were associated with hepatic cholestasis and death before 1 year, which might be explained by a synergistic effect. Remarkably, a patient with an isolated deletion at the 3'-end of SLC6A8 had a similar severe phenotype as seen in BCAP31 deficiency but without deafness. This might be caused by the disturbance of a regulatory element between SLC6A8 and BCAP31.
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van de Kamp
authors.forename: A
authors.initials: A
authors.lastname: Errami
authors.forename: M
authors.initials: M
authors.lastname: Howidi
authors.forename: I
authors.initials: I
authors.lastname: Anselm
authors.forename: S
authors.initials: S
authors.lastname: Winter
authors.forename: J
authors.initials: J
authors.lastname: Phalin-Roque
authors.forename: H
authors.initials: H
authors.lastname: Osaka
authors.forename: S J M
authors.initials: SJ
authors.lastname: van Dooren
authors.forename: G M
authors.initials: GM
authors.lastname: Mancini
authors.forename: S J
authors.initials: SJ
authors.lastname: Steinberg
authors.forename: G S
authors.initials: GS
authors.lastname: Salomons
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003401:Creatine / Q000172:deficiency / Q000235:genetics; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; C091247:BCAP31 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; D003401:Creatine
keywords: X-linked adrenoleukodystrophy; clinical genetics; creatine transporter deficiency; deletion; intellectual disability; liver disease; metabolic disorders; neurology