XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX (Aristaless related homeobox) gene.
BACKGROUND
X-linked mental retardation (XLMR) is the leading cause of mental retardation in males. Mutations in the ARX gene in Xp22.1 have been found in numerous families with both nonsyndromic and syndromic XLMR. The most frequent mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a panel of XLMR families linked to Xp22 was tested for this particular ARX mutation.


METHODS
Genomic DNA from XLMR families linked to Xp22.1 was amplified for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were sized using the ALFexpress automated sequencer.


RESULTS
A panel of 11 families with X-linked mental retardation was screened for the ARX 24dup mutation. Four nonsyndromic XLMR families - MRX29, MRX32, MRX33 and MRX38 - were found to have this particular gene mutation.


CONCLUSIONS
We have identified 4 additional XLMR families with the ARX dup24 mutation from a panel of 11 XLMR families linked to Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily tested for using an automated sequencer, screening should be considered for any male with nonsyndromic MR of unknown etiology.
Stepp
Monica L
ML
J.C. Self Research Institute, Genetic Center, Greenwood, S.C. USA. mdlindsey@ggc.org
Cason
A Lauren
AL
Finnis
Merran
M
Mangelsdorf
Marie
M
Holinski-Feder
Elke
E
Macgregor
David
D
MacMillan
Andrée
A
Holden
Jeanette J A
JJ
Gecz
Jozef
J
Stevenson
Roger E
RE
Schwartz
Charles E
CE
D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors