Expression analysis and mutation detection of DLX5 and DLX6 in autism.
Linkage analysis has reported the chromosomal region 7q21 to be related with autism. This region contains an imprinting region with MECP2-binding sites, and DLX5 is reported to be modulated by MECP2. DLX5 and adjacent DLX6 are homeobox genes working in neurogenesis. From these points, DLX5 and DLX6 are candidate genes for autism. Therefore, we analyzed the expression of DLX5 and DLX6, and also PEG10 as a control in the lymphoblasts of autistic spectrum disorder (ASD) patients by real-time PCR to identify potential abnormality of expression. And we also analyzed DLX5 and DLX6 on ASD patients for mutation by direct sequence. The expression level of DLX5 was not different between ASD and controls but was higher in four ASD patients compared to controls. Clinical features of these four patients were variable. DLX5 expression was biallelic in two ASD patients and two controls, indicating that DLX5 was not imprinted. There was no mutation in DLX5 in ASD. Although DLX5 was not likely to play major role in ASD, genes relating to DLX5 expression and downstream of DLX5 are considered to be candidate genes for some of the ASD patients. In DLX6, we detected a G656A base change (R219H) in two ASD patients who were male siblings. DLX6 may contribute to the pathogenesis of ASD.
Nakashima
Naomi
N
Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Yamagata
Takanori
T
Mori
Masato
M
Kuwajima
Mari
M
Suwa
Kiyotaka
K
Momoi
Mariko Y
MY
D000293:Adolescent; D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
C100596:DLX5 protein, human; C491014:DLX6 protein, human; D018398:Homeodomain Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D014157:Transcription Factors