Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1

Abstract

X-linked intellectual disability (XLID), also known as X-linked mental retardation, is a highly genetically heterogeneous condition for which mutations in >90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation screening in 17 known XLID genes in patients from 135 families and found eight single-nucleotide changes that were absent in controls. For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability.

Figure 1

PQBP1 expression in control and patient lymphoblastoid cell lines. Whole-cell lysates from a control and a patient lymphoblastoid cell line that harbours a truncating mutation in PQBP1 (N143) were run in parallel on an SDS-PAGE gel. The gel was blotted and probed with an antibody specific for the N-terminal part of PQBP1 (α-N1-PQBP1). In the control cell line lysate, a band corresponding to wild-type PQBP1 protein was observed at ∼37 kDa, and in the patient cell line lysate, a truncated PQBP1 protein was observed at ∼22 kDa.