X-linked mental retardation: a comprehensive molecular screen of 47 candidate genes from a 7.4 Mb interval in Xp11.
About 30% of the mutations causing nonsyndromic X-linked mental retardation (MRX) are thought to be located in Xp11 and in the pericentromeric region, with a particular clustering of gene defects in a 7.4 Mb interval flanked by the genes ELK1 and ALAS2. To search for these mutations, 47 brain-expressed candidate genes located in this interval have been screened for mutations in up to 22 mental retardation (MR) families linked to this region. In total, we have identified 57 sequence variants in exons and splice sites of 27 genes. Based on these data, four novel MR genes were identified, but most of the sequence variants observed during this study have not yet been described. The purpose of this article is to present a comprehensive overview of this work and its outcome. It describes all sequence variants detected in 548 exons and their flanking sequences, including disease-causing mutations as well as possibly relevant polymorphic and silent sequence changes. We show that many of the studied genes are unlikely to play a major role in MRX. This information will help to avoid duplication of efforts in the ongoing endeavor to unravel the molecular causes of MRX.
Jensen
Lars Riff
LR
Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Lenzner
Steffen
S
Moser
Bettina
B
Freude
Kristine
K
Tzschach
Andreas
A
Wei
Chen
C
Fryns
Jean-Pierre
JP
Chelly
Jamel
J
Turner
Gillian
G
Moraine
Claude
C
Hamel
Ben
B
Ropers
Hans-Hilger
HH
Kuss
Andreas Walter
AW
D015152:Blotting, Northern; D002460:Cell Line; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D050172:Genes, X-Linked; D006801:Humans; D008214:Lymphocytes; D008297:Male; D038901:X-Linked Intellectual Disability / Q000097:blood / Q000235:genetics*; D009154:Mutation