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

[x-linked adrenoleukodystrophy]

The BCAP 31 gene is located between SLC 6 A 8 , associated with X-linked creatine transporter deficiency , and ABCD 1 , associated with X-linked adrenoleukodystrophy . Recently , loss -of-function mutations in BCAP 31 were reported in association with severe developmental delay , deafness and dystonia . We characterized the breakpoints in eight patients with deletions of SLC 6 A 8 , BCAP 31 and /or ABCD 1 and studied the genotype-phenotype correlations . The phenotype in patients with contiguous gene deletions involving BCAP 31 overlaps with the phenotype of isolated BCAP 31 deficiency . Only deletions involving both BCAP 31 and ABCD 1 were associated with hepatic cholestasis and death before one year , which might be explained by a synergistic effect . Remarkably , a patient with an isolated deletion of the 3 'end of SLC 6 A 8 had a similar severe phenotype as seen in BCAP 31 deficiency but without deafness . This might be caused by disturbance of a regulatory element between SLC 6 A 8 and BCAP 31 .