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

Lars R Jensen; Wei Chen; Bettina Moser; Bettina Lipkowitz; Christopher Schroeder; Luciana Musante; Andreas Tzschach; Vera M Kalscheuer; Ilaria Meloni; Martine Raynaud; Hilde van Esch; Jamel Chelly; Arjan P M de Brouwer; Anna Hackett; Sigrun van der Haar; Wolfram Henn; Jozef Gecz; Olaf Riess; Michael Bonin; Richard Reinhardt; Hans-Hilger Ropers; Andreas W Kuss

doi:10.1038/ejhg.2010.244

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

Eur J Hum Genet. 2011 Jun;19(6):717-20. doi: 10.1038/ejhg.2010.244. Epub 2011 Jan 26.

Affiliation

¹ Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.

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.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins / biosynthesis
Carrier Proteins / genetics*
Chromosomes, Human, X / chemistry
DNA Helicases / biosynthesis
DNA Helicases / genetics*
DNA-Binding Proteins
Female
Genes, X-Linked
Genetic Association Studies
Genetic Testing
High-Throughput Nucleotide Sequencing
Humans
Hybridization, Genetic
Male
Mental Retardation, X-Linked / genetics*
Nerve Tissue Proteins / biosynthesis
Nerve Tissue Proteins / genetics*
Nuclear Proteins / biosynthesis
Nuclear Proteins / genetics*
Pedigree
Plasma Membrane Neurotransmitter Transport Proteins / biosynthesis
Plasma Membrane Neurotransmitter Transport Proteins / genetics*
Polymorphism, Single Nucleotide*
Reverse Transcriptase Polymerase Chain Reaction
X-linked Nuclear Protein

Substances

Carrier Proteins
DNA-Binding Proteins
Nerve Tissue Proteins
Nuclear Proteins
PQBP1 protein, human
Plasma Membrane Neurotransmitter Transport Proteins
SLC6A8 protein, human
DNA Helicases
ATRX protein, human
X-linked Nuclear Protein