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

We report two unrelated patients with overlapping chromosome 2q13 deletions (patient 1 in chr2:111415137-113194067 bp and patient 2 in chr2:110980342-113007823 bp, hg 19). Patient 1 presents with developmental delay, microcephaly and mild dysmorphic facial features, and patient 2 with autism spectrum disorder, borderline cognitive abilities, deficits in attention and executive functions and mild dysmorphic facial features. The mother and maternal grandmother of patient 1 were healthy carriers of the deletion. Previously, 2q13 deletions were reported in 27 patients, and the interpretation of its clinical significance varied. Our findings support that the 2q13 deletion is associated with a developmental delay syndrome manifesting with variable expressivity and reduced penetrance which poses a challenge for genetic counselling as well as the clinical recognition of 2q13 deletion patients.

• Klíčová slova
• 2q13 deletion, BCL2L11, Developmental delay, FBLN7, Facial dysmorphism, TMEM87B, aCGH,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH