Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1

• Published in: Clinical genetics Vol. 87; no. 2; pp. 141 - 147
• Main Authors: van de Kamp, J.M., Errami, A., Howidi, M., Anselm, I., Winter, S., Phalin-Roque, J., Osaka, H., van Dooren, S.J.M., Mancini, G.M., Steinberg, S.J., Salomons, G.S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2015
• Subjects: Adrenoleukodystrophy - genetics; Adrenoleukodystrophy - mortality; Adrenoleukodystrophy - pathology; Adult; ATP Binding Cassette Transporter, Sub-Family D, Member 1; ATP-Binding Cassette Transporters - genetics; Brain Diseases, Metabolic, Inborn - genetics; Brain Diseases, Metabolic, Inborn - mortality; Brain Diseases, Metabolic, Inborn - pathology; Child; Child, Preschool; Cholestasis, Intrahepatic - genetics; Cholestasis, Intrahepatic - mortality; Cholestasis, Intrahepatic - pathology; clinical genetics; Creatine - deficiency; Creatine - genetics; creatine transporter deficiency; deletion; Developmental disabilities; Gene Deletion; Genetic Association Studies; Genetic disorders; Genotype & phenotype; Humans; Infant; Infant, Newborn; intellectual disability; Intellectual Disability - genetics; Intellectual Disability - mortality; Intellectual Disability - pathology; liver disease; Male; Membrane Proteins - genetics; Mental Retardation, X-Linked - genetics; Mental Retardation, X-Linked - mortality; Mental Retardation, X-Linked - pathology; metabolic disorders; Mutation; Nerve Tissue Proteins - genetics; neurology; Phenotype; Plasma Membrane Neurotransmitter Transport Proteins - deficiency; Plasma Membrane Neurotransmitter Transport Proteins - genetics; X-linked adrenoleukodystrophy; metabolic disorders; creatine transporter deficiency; liver disease; deletion; X-linked adrenoleukodystrophy; clinical genetics; intellectual disability; neurology
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.12355

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.