Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1.
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.
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Lars R
LR
Jensen
Wei
W
Chen
Bettina
B
Moser
Bettina
B
Lipkowitz
Christopher
C
Schroeder
Luciana
L
Musante
Andreas
A
Tzschach
Vera M
VM
Kalscheuer
Ilaria
I
Meloni
Martine
M
Raynaud
Hilde
H
van Esch
Jamel
J
Chelly
Arjan P M
AP
de Brouwer
Anna
A
Hackett
Sigrun
S
van der Haar
Wolfram
W
Henn
Jozef
J
Gecz
Olaf
O
Riess
Michael
M
Bonin
Richard
R
Reinhardt
Hans-Hilger
HH
Ropers
Andreas W
AW
Kuss
D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000737:chemistry; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D050172:Genes, X-Linked; D056726:Genetic Association Studies; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006824:Hybridization, Genetic; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010375:Pedigree; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075924:X-linked Nuclear Protein
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
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