BACKGROUND: Recent studies suggest that duplication of the 9p24.3 chromosomal locus, which includes the DOCK8 and KANK1 genes, is associated with autism spectrum disorders (ASD), intellectual disability/developmental delay (ID/DD), learning problems, language disorders, hyperactivity, and epilepsy. Correlation between this duplication and the carrier phenotype needs further discussion. METHODS: In this study, three unrelated patients with ID/DD and ASD underwent SNP aCGH and MLPA testing. Similarities in the phenotypes of patients with 9p24.3, 15q11.2, and 16p11.2 duplications were also observed. RESULTS: All patients with ID/DD and ASD carried the 9p24.3 duplication and showed intragenic duplication of DOCK8. Additionally, two patients had ADHD, one was hearing impaired and obese, and one had macrocephaly. Inheritance of the 9p24.3 duplication was confirmed in one patient and his sibling. In one patient KANK1 was duplicated along with DOCK8. Carriers of 9p24.3, 15q11.2, and 16p11.2 duplications showed several phenotypic similarities, with ID/DD more strongly associated with duplication of 9p24.3 than of 15q11.2 and 16p11.2. CONCLUSION: We concluded that 9p24.3 is a likely cause of ASD and ID/DD, especially in cases of DOCK8 intragenic duplication. DOCK8 is a likely causative gene, and KANK1 aberrations a modulator, of the clinical phenotype observed. Other modulators were not excluded.

• Klíčová slova
• 15q11.2 duplication, 16p11.2 duplication, 9p24.3 duplication, developmental delay,
• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• chromozomální poruchy genetika   patologie   MeSH
• cytoskeletální proteiny genetika   MeSH
• dítě MeSH
• duplikace chromozomů * MeSH
• fenotyp * MeSH
• lidé MeSH
• lidské chromozomy, pár 9 genetika   MeSH
• předškolní dítě MeSH
• výměnné faktory guaninnukleotidů genetika   MeSH
• vývojové poruchy u dětí genetika   patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• cytoskeletální proteiny MeSH
• DOCK8 protein, human MeSH Prohlížeč
• KANK1 protein, human MeSH Prohlížeč
• výměnné faktory guaninnukleotidů MeSH

OBJECTIVES: The term "copy number variation/variant" (CNV) denotes a DNA sequence with a magnitude of 1 kb at least which is differently represented among individuals based on its deletion or duplication. Since 2008, multiple studies have reported copy number variations in schizophrenia, and they seem to fill in a gap in our knowledge on the genetic background of schizophrenia. The aim of this review is to sum up the current findings related to CNVs in schizophrenia in order to facilitate further research. METHODS: We searched the PubMed computer database using the key words "schizophrenia AND CNVs" on 26th October 2011. Out of 91 obtained results, we selected the references based on their relevance. RESULTS: The CNVs at genome loci 1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, 16p13.1 and 22q11.2 were associated with schizophrenia most frequently. The data provide evidence for low prevalent, but highly penetrant CNVs associated with schizophrenia. CNV deletions show higher penetrance than duplications. Larger CNVs often have higher penetrance than smaller CNVs. Although the vast majority of CNVs are inherited, CNVs that have newly occurred as de novo mutations have more readily been implicated in schizophrenia. De novo CNVs may be responsible for the presence of schizophrenia in only one of the two monozygotic twins, who otherwise have identical genomes. CONCLUSION: Identifying CNVs in schizophrenia can lead to changes in the treatment and genetic counselling. Our knowledge on the genetic background of neurodevelopmental disorders may also reduce stigma in schizophrenia.

• MeSH
• celogenomová asociační studie statistika a číselné údaje   MeSH
• genetická predispozice k nemoci genetika   MeSH
• genom lidský genetika   MeSH
• lidé MeSH
• schizofrenie genetika   MeSH
• variabilita počtu kopií segmentů DNA genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH