A translocation t(6;7)(p11-p12;q22) associated with autism and mental retardation: localization and identification of candidate genes at the breakpoints.
OBJECTIVE
Our aim is to use information from cytogenetic anomalies to identify candidate genes for autism.


METHODS
We have identified a male patient with mental retardation and autism who has a balanced translocation involving chromosomes 6 and 7, described as t(6;7)(p11-p12;q22). This translocation was inherited from an apparently normal father.


RESULTS
Using fluorescence in situ hybridization, we have localized the breakpoints on both the chromosomes; and using bioinformatic genomic analysis, we have identified a number of potential candidate genes at these loci. These include the neural pentraxin 2 gene, NPTX2, and a novel gene encoding a transmembrane protein, TMEM130, which contains a polycystic kidney domain on 7q22. On 6p12 the breakpoint directly interrupts isoform 2 of the human homologue of the mouse dystonin gene. We also performed a 250 K single nucleotide polymorphism microarray analysis and comparative genomic hybridization using a bacterial artificial chromosome microarray to look for minor genomic deletions or duplications in the proband's DNA. The single nucleotide polymorphism microarray analysis identified a number of copy number variants, remote from the translocation breakpoints, containing potential candidate genes.


CONCLUSIONS
It is conceivable that one or more of the copy number variant regions or either of the two breakpoint locations and the dystonin gene, in particular, may be a new locus for a form of mental retardation, which may also include autistic features.
Vincent
John B
JB
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada. john_vincent@camh.net
Choufani
Sanaa
S
Horike
Shin-ichi
S
Stachowiak
Beata
B
Li
Martin
M
Dill
Fred J
FJ
Marshall
Christian
C
Hrynchak
Monica
M
Pewsey
Elizabeth
E
Ukadike
Kennedy C
KC
Friedman
Jan M
JM
Srivastava
Anand K
AK
Scherer
Stephen W
SW
D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D019457:Chromosome Breakage; D022202:Chromosomes, Artificial, Bacterial; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014178:Translocation, Genetic; D000099153:Pentraxins
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D000099153:Pentraxins