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Genotype–phenotype correlation of contiguous gene deletions of SLC6A8 , BCAP31 and ABCD1
Author(s) -
van de Kamp J.M.,
Errami A.,
Howidi M.,
Anselm I.,
Winter S.,
PhalinRoque J.,
Osaka H.,
van Dooren S.J.M.,
Mancini G.M.,
Steinberg S.J.,
Salomons G.S.
Publication year - 2015
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12355
Subject(s) - phenotype , genetics , biology , adrenoleukodystrophy , genotype phenotype distinction , genotype , gene , mutation , peroxisome
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 .