Summary
The dataset provides evidence of the pathogenic role of ARID1B haploinsufficiency in human disease, supported by a description of a male patient presenting with developmental delay, speech impairment, mild dysmorphic features, and borderline intellectual disability. The identified mutation in this patient is a de novo balanced translocation, t(5;6)(q11;q25.3), leading to disruption of ARID1B at the breakpoint, with potential null or loss-of-function consequences, as confirmed by parental testing. This mutation exemplifies the case-level evidence suggesting that haploinsufficiency of ARID1B is a significant factor in the clinical phenotype of individuals affected by the associated disease. Furthermore, the synthesis of this case with a review of literature and clinical observations substantiates the association of ARID1B haploinsufficiency with a spectrum of disorders including intellectual disabilities, corpus callosum abnormalities, Coffin-Siris syndrome, and autism. These functional studies collectively contribute to our understanding of the critical role ARID1B plays in neurodevelopment and associated pathologies.
Evidence of Haploinsufficiency
Patient Identifier: the present patient
Mutation Type: balanced translocation
Mutation Details: a de novo balanced t(5;6)(q11;q25.3)
Clinical Phenotype: developmental delay, speech impairment, mild dysmorphic features, and borderline intellectual disability
Inheritance Tested: Yes
Effect on Gene Function: disruption at the translocation breakpoint, no fusion transcripts could be formed
Direct Quote: "we report on a male patient with developmental delay, speech impairment, mild dysmorphic features, and borderline intellectual disability, bearing a de novo balanced t(5;6)(q11;q25.3). By combining FISH and long distance inverse PCR, we identified two genes, ADAMTS6 and ARID1B, which were disrupted at the translocation breakpoints."
Location in Paper: Abstract
Clinical Features
Feature: developmental delay
Frequency: N/A
Direct Quote: "we conclude that the most prominent and consistent clinical findings in patients with ARID1B haploinsufficiency are developmental delay"
Location in Paper: Abstract
Feature: speech impairment
Frequency: N/A
Direct Quote: "the most prominent and consistent clinical findings in patients with ARID1B haploinsufficiency are ... speech impairment"
Location in Paper: Abstract
Feature: intellectual disability
Frequency: N/A
Direct Quote: "the most prominent and consistent clinical findings in patients with ARID1B haploinsufficiency are ... intellectual disability"
Location in Paper: Abstract
Functional Studies
Study Type: review of literature and clinical observations
Methodology: review of patients with ARID1B mutations
Conclusions: haploinsufficiency of ARID1B is associated with intellectual disabilities with or without corpus callosum abnormalities, Coffin–Siris syndrome and autism
Direct Quote: "ARID1B haploinsufficiency has already been described in patients with intellectual disabilities with or without corpus callosum abnormalities, Coffin–Siris syndrome and autism (OMIM 614562 and OMIM 614556)."
Location in Paper: Abstract