The CASK gene harbored in a deletion detected by array-CGH as a potential candidate for a gene causative of X-linked dominant mental retardation.
Here we report on a 5-year-old Japanese girl with developmental delay and microcephaly. Although she had a normal karyotype, a bacterial artificial chromosome-based array-comparative genome hybridization analysis detected a de novo 4.0-Mb heterozygous deletion at Xp11.3-p11.4 harboring nine genes. By comparison with a healthy carrier mother of a boy with atypical Norrie disease having a smaller deletion in the same region, we excluded four genes as candidates whose haploinsufficiency would be causative for developmental delay. Among the other five genes, CASK seems to be the most likely candidate for a causative gene, because it is strongly expressed in fetal brain and plays important roles in neural development and synaptic function. We confirmed that the expression of CASK mRNA was decreased in the patient compared with healthy controls and the patient's X-chromosomal inactivation was not skewed. These results suggested that the genetic deletion of CASK results in haploinsufficiency, which might be causative for the patient's developmental delay or mental retardation. (c) 2008 Wiley-Liss, Inc.
Hayashi
Shin
S
Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Mizuno
Seiji
S
Migita
Ohsuke
O
Okuyama
Torayuki
T
Makita
Yoshio
Y
Hata
Akira
A
Imoto
Issei
I
Inazawa
Johji
J
D002675:Child, Preschool; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial; D041321:Chromosomes, Human, X / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D049951:X Chromosome Inactivation
D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins; C106868:CASK kinases; D051528:Guanylate Kinases