ARID1A

Molecular characteristics

Genetic counselling: Mutations in ARID1A are inherited in an autosomal dominant manner, but to date all cases result from a de novo mutation. Thus, the affected individuals represent sporadic cases, i.e., a single occurrence in a family. The recurrence risk for future pregnancies is considered low (probably <1%). No individuals with ARID1A-related intellectual disability have been known to reproduce. Prenatal testing is technically feasible, but based upon the current knowledge the likelihood of recurrence in families who have had an affected child is considered low.

Thus far, eight patients with mutations in ARID1A have been described. All of these were truncating mutations, and five were mosaic. It has been suggested that full mutations could be lethal, but this remains to be proven.

Although somatic ARID1A mutations are frequently identified in tumours there is no clear evidence of an increased risk of tumours in Coffin-Siris syndrome patients. Further data collection is necessary to make firm conclusions regarding this important issue.